Perhaps it is worth putting some perspective into the Al debate and the
role of Zn in Alzheimer's disease.
While the role of Al is still debated, the majority of Alzheimer's
researchers believe that Al is not the cause of the disease. There
are four major reasons for this belief.
First, although Al is neurotoxic,
the levels which were required to produce the toxic effects in laboratory
animals were far greater than those experienced by most people in
everyday life. Hence, moderate exposure to Al in the environment should
not be neurotoxic.
Second, while Al causes neurofibrillar degeneration in the brain, the
types of filaments that are produced differ from those seen in Alzheimer's
disease.
Third, other neuropathological features of Alzheimer's disease such as
amyloid plaques are not seen in Al toxicity.
Fourth, and probably most importantly, there are now some real clues as
to the risk factors (e.g. apolipoprotein E allotype) which contribute both to early and late-onset Alzheimer's
disease. These risk factors are unrelated to Al.
>The role of Zn in Alzheimer's disease is highly contentious. Zn has recently
been shown by Bush et al. to cause precipitation of the amyloid protein
in the form of fibrils. This study was performed in the test tube, and
it is difficult to know to what extent it could occur in vivo. We do
not know what the levels of FREE Zn are in the brain. Nor is it clear
to what extent dietary Zn influences the levels of Zn which are stored
in susceptible structure of the brain such as the hippocampus.
While Zn must be considered as a possible factor, its role is still very unclear.
The danger is that old people may shy away from taking Zn supplements. It
is well established that Zn deficiency is common in the aged.
For more information on Alzheimer's disease and its causes, see
Alzheimer Web: http://werple.mira.net.au/~dhs/ad.html.
David Small
NH&MRC Research Fellow
Dept. of Pathology
University of Melbourne
> [this thread was originally about what sorts of materials to make
> pipes, etc., out of.. i'm continuing discussion on a specific topic
> of this thread]
>> In article <7MAR199517370817 at cvax.psi.ch>,
> Dr Ivan D Reid, µSR Facility, PSI <reid at cvax.psi.ch> wrote:
> >In article <3j64du$4tr at otis.netspace.net.au>,
> > zodiac at zodiac@insane.apana.org.au writes...
> >>I understood fairly recent studies have shown that aluminium is NOT a
> >>cause of ALZHEIMERS, and that zinc is now considered the culprit.
> >
> > The first part of your statement is true. The original study linking
> >Alzheimer's and aluminium has been withdrawn; they discovered that the Al
> >that they'd detected was an experimental artifact. I haven't heard of
> >anything implicating zinc, though.
>> I don't want to start a flame war, but are you sure about this?
>> I told that to my neuropharmacology teacher last semester and he
> said that there really was significant evidence about Al accumulation
> at certain kinds of neural tissue. (neurofibrillary tangles and
> another kind of tissue which I forgot)
>> ...So, I did a mini-lit search w/medline and came up with the following
> references.. Al is _very_ neurotoxic (in many ways unrelated to
> alzheimers), but also there is quite a bit of evidence linking
> Al to alzheimers.
>> I guess the point to be debated is whether or long-term exposure increases
> the susceptibility to Alzheimers.. The jury is still out, I think.
>> Btw: does anyone have the reference of the researchers who withdrew
> their data, or know the name of these researchers?
>> -marc anderson
>andersom at benji.colorado.edu>> 1
> AU - Shen ZM
> AU - Perczel A
> AU - Hollosi M
> AU - Nagypal I
> AU - Fasman GD
> TI - Study of Al3+ binding and conformational properties of the alanine-
> substituted C-terminal domain of the NF-M protein and its relevance
> to Alzheimer's disease.
> AB - NF-M13 [H-(Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val-Glu-Glu-Lys-Gly)-OH],
> NF-M17 [H-(Glu-Glu-Lys-Gly-Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val-Glu-
> Glu-Lys-Gly) -OH], and their phosphorylated derivatives, representing
> the C-terminal phosphorylation domain of the neurofilament protein
> midsize subunit, have four possible binding sites for metal ions: the
> COO- group of glutamate, the OH group of the serine residue, the PO3H-
> group of phosphoserine (when present), and the COO- at the terminus
> of the peptide chain. The CD titration of the phosphorylated
> neurofilament fragments with Al3+ and Ca2+ yielded a significant
> conformational change that resulted in conformations containing high
> beta-pleated-sheet contents, which precipitate on standing
> (intermolecular complex). Al3+ binding to the unphosphorylated NF-M13
> and NF-M17 did not exhibit this behavior. Several alanine analogues
> of the parent NF-M17 peptide were synthesized in order to determine
> the relationship between metal ions and possible binding sites. CD
> titration of analogues with Ca2+ indicated that the critical residues
> of NF-M17 for Ca(2+)-induced conformational changes, from random to
> beta-pleated sheet, are the N-terminal serine or both phosphorylated
> serines. Al(3+)-induced conformational changes suggest that the
> critical sites of NF-M17 yielding the beta-pleated-sheet structure
> are the four glutamates or phosphorylated serines, especially the C-
> terminal SerP. On the basis of the titration data, it is very likely
> that analogues with a serine in position 11 form a stable
> intramolecular complex with Al3+ that, however, does not result in
> the adoption of the beta-conformation. Back-titration with citric
> acid fails to reverse the Al(3+)-induced conformational changes of
> the phosphorylated peptides. The above results, especially the
> possible formation of intramolecular and intermolecular Al3+
> complexes, may have relevance to the molecular mechanism, through
> which the neurotoxin Al3+ gives rise to the formation of
> neurofilament tangles.
> AD - Department of Biochemistry
> AD - Brandeis University
> AD - Waltham
> AD - Massachusetts 02254-9110.
> SO - Biochemistry 1994 Aug 16;33(32):9627-36
> DP - 1994 Aug 16
> TA - Biochemistry
> PG - 9627-36
> IP - 32
> VI - 33
> IS - 0006-2960
> UI - 94347732
>> 2
> AU - Naylor GJ
> AU - Sheperd B
> AU - Treliving L
> AU - McHarg A
> AU - Smith A
> AU - Ward N
> AU - Harper M
> TI - Tissue aluminum concentrations stability over time, relationship to
> age, and dietary intake.
> AB - Aluminum concentration was measured in serum, whole blood, hair, and
> urine by neutron activation analysis. Seventy-six nondemented
> subjects were investigated. Not all assays were done on all subjects
> (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42
> subjects), but tissue aluminum concentrations were estimated on more
> than one occasion on 32 subjects. The mean +/- SD aluminum
> concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in
> whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/-
> 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g
> (N = 42). Using product moment correlation coefficient there was no
> significant correlation between age and tissue aluminum
> concentrations, nor between dietary intake of aluminum and tissue
> aluminum. The tissue aluminum concentrations were not stable over
> time even when dietary intake was constant. Tissue aluminum
> concentrations were measured in 14 patients after 7 days of dietary
> control and repeated approximately 6 weeks later, again after 7 days
> of dietary control. There was no significant correlation between the
> two estimations in any tissue measured. These results suggest that
> raised tissue aluminum concentrations reported in Alzheimer's disease
> are not an exaggeration of a normal ageing process, are not likely to
> be simply secondary to increased dietary aluminum intake, and that
> Alzheimer's disease does not represent the chronic toxic effect of
> moderately raised aluminum levels at the upper end of the normal
> distribution.
> AD - Royal Dundee Liff Hospital
> AD - Dundee
> AD - U.K.
> SO - Biol Psychiatry 1990 Apr 15;27(8):884-90
> DP - 1990 Apr 15
> TA - Biol Psychiatry
> PG - 884-90
> IP - 8
> VI - 27
> IS - 0006-3223
> UI - 90234774
>> 3
> AU - Crapper DR
> AU - Krishnan SS
> AU - Quittkat S
> TI - Aluminium, neurofibrillary degeneration and Alzheimer's disease.
> AB - Aluminium is neurotoxic and results in the proliferation of 100 A
> diameter filaments in the cytoplasm of certain neurons. The aluminium
> concentration for 7 normal human brains was 1-9 +/- 0-7 SD mug/g dry
> weight (n = 208 samples). The aluminium content of 585 areas sampled
> in 10 post-mortem cases of Alzheimer's disease ranging in age from 50
> to 88 years, in which the diagnosis was based on the specific
> histological appearances, revealed an elevated aluminium content in
> some regions. A range of 0-4 - 107-0 mug/g was encountered and 28 per
> cent of all regions sampled had concentrations in excess of 4 mug/g.
> Five of 6 cerebral biopsies from patients with Alzheimer's disease
> also had elevated aluminium content. In 2 additional Alzheimer's
> brains with neurofibrillary degeneration restricted to certain
> anatomical areas, elevated aluminium content was found to be
> associated with neurofibrillary degeneration and not with senile
> plaques. Furthermore, elevated aluminium content in multiple cortical
> regions was not found in 2 vascular dementias of the elderly. While
> the cytotoxic concentration for human neurons is unknown, the
> cytotoxic concentration for cat's cerebral neurons appears to lie
> between 4 and 6 mug/g dry weight.
> SO - Brain 1976 Mar;99(1):67-80
> DP - 1976 Mar
> TA - Brain
> PG - 67-80
> IP - 1
> VI - 99
> IS - 0006-8950
> UI - 77001142
>> 4
> AU - Joshi JG
> TI - Neurochemical hypothesis: participation by aluminum in producing
> critical mass of colocalized errors in brain leads to neurological
> disease.
> AB - 1. Aluminum is an established neurotoxin. Prolonged exposure to even
> low levels of aluminum permit its chelation and subsequent transport
> to brain where it is non-uniformly distributed. 2. Available evidence
> suggests that (i) aluminum interferes with glucose metabolism by
> inhibiting hexokinase and glucose-6-phosphate dehydrogenase; (ii) it
> binds to calmodulin and affects numerous phosphorylation-
> dephosphorylation reactions; (iii) it binds to transferrin and
> ferritin, affects the function of these proteins which in turn affect
> iron metabolism. 3. Thus accumulation of aluminum-induced metabolic
> errors colocalized in specific areas of the brain may lead to
> neurological disorders.
> AD - Department of Biochemistry
> AD - University of Tennessee
> AD - Knoxville 37996-0840.
> SO - Comp Biochem Physiol [C] 1991;100(1-2):103-5
> DP - 1991
> TA - Comp Biochem Physiol [C]
> PG - 103-5
> IP - 1-2
> VI - 100
> IS - 0742-8413
> UI - 91322981
>> 5
> AU - Eichhorn GL
> TI - Is there any relationship between aluminum and Alzheimer's disease?
> AB - The controversial role of aluminum in Alzheimer's disease (AD) is
> reviewed. While current data would suggest the lack of a causative
> role, alterations in the brain and other organ systems caused by AD
> might increase the penetration of aluminum as well as other metals
> into the brain and lead to their contribution to such pathological
> features as neurofibrillar tangles (NFTs).
> AD - National Institutes of Health
> AD - National Institute on Aging
> AD - Laboratory of Cellular and Molecular Biology
> AD - Baltimore
> AD - Maryland 21224.
> SO - Exp Gerontol 1993 Jul-Oct;28(4-5):493-8
> DP - 1993 Jul-Oct
> TA - Exp Gerontol
> PG - 493-8
> IP - 4-5
> VI - 28
> IS - 0531-5565
> UI - 94039611
>> 6
> AU - Farrar G
> AU - Altmann P
> AU - Welch S
> AU - Wychrij O
> AU - Ghose B
> AU - Lejeune J
> AU - Corbett J
> AU - Prasher V
> AU - Blair JA
> TI - Defective gallium-transferrin binding in Alzheimer disease and Down
> syndrome: possible mechanism for accumulation of aluminium in brain
> [see comments]
> AB - The plasma distribution of gallium (as an analogue of aluminium) was
> investigated in patients with Alzheimer disease, Down syndrome, or
> stroke dementia, in subjects on haemodialysis for chronic renal
> failure, and in healthy controls. Gallium-transferrin binding was
> significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down
> syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%),
> whereas stroke dementia and haemodialysis patients had normal
> binding. There were no differences among the groups in plasma citrate
> concentration. The plasma transferrin concentration was slightly
> lower in the Alzheimer and Down syndrome groups than in the controls,
> but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98
> [0.18] g/l in controls). Transferrin iron saturation was higher in
> the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the
> controls (39.0%) or stroke dementia patients (33.4%). This deficiency
> of gallium/aluminium binding would leave more unbound aluminium which
> could move readily into the brain, where it has neurotoxic effects.
> AD - Division of Biology
> AD - University of Aston
> AD - Birmingham
> AD - UK.
> SO - Lancet 1990 Mar 31;335(8692):747-50
> DP - 1990 Mar 31
> TA - Lancet
> PG - 747-50
> IP - 8692
> VI - 335
> IS - 0023-7507
> UI - 90205330
>> 7
> AU - Martyn CN
> AU - Barker DJ
> AU - Osmond C
> AU - Harris EC
> AU - Edwardson JA
> AU - Lacey RF
> TI - Geographical relation between Alzheimer's disease and aluminum in
> drinking water [see comments]
> AB - In a survey of eighty-eight county districts within England and
> Wales, rates of Alzheimer's disease in people under the age of 70
> years were estimated from the records of the computerised tomographic
> (CT) scanning units that served these districts. Rates were adjusted
> to compensate for differences in distance from the nearest CT
> scanning unit and for differences in the size of the population
> served by the units. Aluminium concentrations in water over the past
> 10 years were obtained from water authorities and water companies.
> The risk of Alzheimer's disease was 1.5 times higher in districts
> where the mean aluminium concentration exceeded 0.11 mg/l than in
> districts where concentrations were less than 0.01 mg/l. There was no
> evidence of a relation between other causes of dementia, or epilepsy,
> and aluminium concentrations in water.
> AD - Medical Research Council Environmental Epidemiology Unit
> AD - Southampton General Hospital.
> SO - Lancet 1989 Jan 14;1(8629):59-62
> DP - 1989 Jan 14
> TA - Lancet
> PG - 59-62
> IP - 8629
> VI - 1
> IS - 0023-7507
> UI - 89082166
>> 8
> AU - Banks WA
> AU - Kastin AJ
> TI - Aluminium increases permeability of the blood-brain barrier to
> labelled DSIP and beta-endorphin: possible implications for senile
> and dialysis dementia.
> AB - The primary lesion in Alzheimer's disease and dialysis dementia has
> been postulated to be an impaired blood-brain-barrier (BBB)
> permeability that allows neurotoxins like aluminium to reach the
> central nervous system. The present study shows that aluminium itself
> affects the permeability of the BBB of rats to small peptides.
> Intraperitoneal injection of aluminium chloride increased the
> permeability of the BBB to iodinated N-Tyr-delta-sleep-inducing
> peptide and beta-endorphin by 60-70%. Thus, aluminium can affect the
> BBB in ways that might be involved in dementia.
> SO - Lancet 1983 Nov 26;2(8361):1227-9
> DP - 1983 Nov 26
> TA - Lancet
> PG - 1227-9
> IP - 8361
> VI - 2
> IS - 0023-7507
> UI - 84066730
>> 9
> AU - Hollosi M
> AU - Shen ZM
> AU - Perczel A
> AU - Fasman GD
> TI - Stable intrachain and interchain complexes of neurofilament peptides:
> a putative link between Al3+ and Alzheimer disease.
> AB - The etiologic role of Al3+ in Alzheimer disease has been
> controversial. Circular dichroism (CD) spectroscopic studies on two
> synthetic fragments of human neurofilament protein mid-sized subunit
> (NF-M), NF-M13 (KSPVPKSPVEEKG) and NF-M17 (EEKGKSPVPKSPVEEKG), and
> their alanine-substituted and/or serine-phosphorylated derivatives
> were carried out in an attempt to find a molecular mechanism for the
> effect of Al3+ to induce aggregation of neuronal proteins or their
> catabolic fragments. Al3+ and Ca2+ ions were found to induce beta-
> pleated sheet formation in the phosphorylated fragments. The cation
> sensitivity depended on the length and charge distribution of the
> sequence and site of phosphorylation. Al3+-induced conformational
> changes were irreversible to citric acid chelation, whereas Ca(2+)-
> induced conformational changes were reversible with citric acid.
> Studies of the alanine derivatives demonstrated which residues
> affected Al3+ or Ca2+ binding. Peptides containing at least one free
> (nonphosphorylated) serine residue were shown to form an
> intramolecular Al3+ complex, rather than an intermolecular one. In
> the intramolecular (intrachain) complex, the ligand function of the
> deprotonated serine hydroxyl was delineated [(Al.pepH-1)-type
> complex]. Ca2+ ions did not show a tendency for intramolecular
> complexing. The potential role of Al3+ in Alzheimer disease tangle
> and plaque formation is strongly suggested.
> AD - Department of Organic Chemistry
> AD - Eotvos University Budapest
> AD - Hungary.
> SO - Proc Natl Acad Sci U S A 1994 May 24;91(11):4902-6
> DP - 1994 May 24
> TA - Proc Natl Acad Sci U S A
> PG - 4902-6
> IP - 11
> VI - 91
> IS - 0027-8424
> UI - 94255436
>> 10
> AU - Clauberg M
> AU - Joshi JG
> TI - Regulation of serine protease activity by aluminum: implications for
> Alzheimer disease.
> AB - The brain of Alzheimer disease patients contains plaques that are
> diagnostic for the disease. The plaques also contain beta-amyloid
> peptide, alpha 1-antichymotrypsin, and the element aluminum. We
> present indirect evidence that can relate all three components of
> plaques to each other in such a way as to suggest their involvement
> in the etiology of the disease. The beta-amyloid peptide is derived
> by proteolytic processing from beta-amyloid precursor proteins and
> some of these proteins contain a domain that is highly homologous to
> bovine pancreatic trypsin inhibitor. Bovine pancreatic trypsin
> inhibitor also inhibits alpha-chymotrypsin and we show that aluminum
> affects both the activity and the inhibition of this enzyme. At pH
> 6.5, in the presence of aluminum, the enzyme activity is doubled, and
> the inhibitor is only 1% as effective as in the absence of the metal
> ion. The inhibition by BX-9, a protease inhibitor prepared from
> protein components of amyloid plaques, is also reduced by aluminum;
> so too is that by alpha 1-antichymotrypsin but to a lesser degree. In
> the Alzheimer brain, we propose that aluminum may accelerate
> proteolytic processing of the beta-amyloid precursor protein by
> suppression of the inhibitor domain. Thus, the beta-amyloid peptide
> may accumulate and initiate plaque formation.
> AD - Department of Biochemistry
> AD - University of Tennessee
> AD - Knoxville 37996-0840.
> SO - Proc Natl Acad Sci U S A 1993 Feb 1;90(3):1009-12
> DP - 1993 Feb 1
> TA - Proc Natl Acad Sci U S A
> PG - 1009-12
> IP - 3
> VI - 90
> IS - 0027-8424
> UI - 93157332
>> 11
> AU - Domingo JL
> AU - Gomez M
> AU - Sanchez DJ
> AU - Llobet JM
> AU - Corbella J
> TI - Effect of various dietary constituents on gastrointestinal absorption
> of aluminum from drinking water and diet.
> AB - The influence of some frequent dietary constituents on
> gastrointestinal absorption of aluminum from drinking water and diet
> was investigated in mice. Eight groups of male mice received lactic
> (57.6 mg/kg/day), tartaric (96 mg/kg/day), gluconic (125.4
> mg/kg/day), malic (85.8 mg/kg/day), succinic (75.6 mg/kg/day),
> ascorbic (112.6 mg/kg/day), citric (124 mg/kg/day), and oxalic (80.6
> mg/kg/day) acids in the drinking water for one month. At the end of
> this period, animals were killed and aluminum concentrations in
> liver, spleen, kidney, brain, and bone were determined. All the
> dietary constituents significantly increased the aluminum levels in
> bone, whereas brain aluminum concentrations were also raised by the
> intake of lactic, gluconic, malic, citric, and oxalic acids. The
> levels of aluminum found in spleen were significantly increased by
> gluconic and ascorbic acids, whereas gluconic and oxalic acids also
> raised the concentrations of aluminum found in kidneys. Because of
> the wide presence and consumption of the above dietary constituents,
> in order to prevent aluminum accumulation and toxicity we suggest a
> drastic limitation of human exposure to aluminum.
> AD - Laboratory of Toxicology and Biochemistry
> AD - School of Medicine
> AD - University of Barcelona
> AD - Reus
> AD - Spain.
> SO - Res Commun Chem Pathol Pharmacol 1993 Mar;79(3):377-80
> DP - 1993 Mar
> TA - Res Commun Chem Pathol Pharmacol
> PG - 377-80
> IP - 3
> VI - 79
> IS - 0034-5164
> UI - 93242227
>> 12
> AU - Good PF
> AU - Perl DP
> AU - Bierer LM
> AU - Schmeidler J
> TI - Selective accumulation of aluminum and iron in the neurofibrillary
> tangles of Alzheimer's disease: a laser microprobe (LAMMA) study.
> AB - We report the results of an examination of the elemental content of
> neurofibrillary tangle-bearing and neurofibrillary tangle-free
> neurons identified within the hippocampus of 10 subjects with
> Alzheimer's disease and 4 neuropathologically intact age-matched
> control subjects. The study employed laser microprobe mass analysis
> (LAMMA), a technique that provides extremely sensitive multielement
> detection in plastic-embedded, semithin-sectioned tissues. Evidence
> for the selective accumulation of aluminum within the neurofibrillary
> tangle-bearing neurons was obtained in all 10 subjects with
> Alzheimer's disease. The site of aluminum deposition within these
> cells was the neurofibrillary tangle itself, and not the "nuclear
> region," as we previously reported. Iron accumulation was also
> detected within neurofibrillary tangles. Evaluation for the
> accumulation of other elements within the tangle-bearing neurons
> failed to reveal any other metallic element as being consistently
> present. In addition, probe sites directed to neurons identified in
> snap-frozen cryostat sections from 2 subjects with Alzheimer's
> disease revealed similar spectra with prominent aluminum-related
> peaks, confirming that our findings are not related to exogenous
> contamination through fixation, embedding, or other procedures prior
> to analysis. This study further confirms the association of aluminum
> and neurofibrillary tangle formation in Alzheimer's disease.
> AD - Department of Pathology
> AD - Mount Sinai School of Medicine
> AD - New York
> AD - NY 10029.
> SO - Ann Neurol 1992 Mar;31(3):286-92
> DP - 1992 Mar
> TA - Ann Neurol
> PG - 286-92
> IP - 3
> VI - 31
> IS - 0364-5134
> UI - 92344346
>> 13
> AU - DeKosky ST
> AU - Harbaugh RE
> AU - Schmitt FA
> AU - Bakay RA
> AU - Chui HC
> AU - Knopman DS
> AU - Reeder TM
> AU - Shetter AG
> AU - Senter HJ
> AU - Markesbery WR
> TI - Cortical biopsy in Alzheimer's disease: diagnostic accuracy and
> neurochemical, neuropathological, and cognitive correlations.
> Intraventricular Bethanecol Study Group.
> AB - Neurochemical assessments were performed on biopsy samples taken from
> the right frontal lobe of patients diagnosed with Alzheimer's disease
> (AD), before the implantation of a ventricular catheter and pump
> assembly for the infusion of bethanechol chloride as an experimental
> therapy. The pathologically diagnosed patients with AD (n = 35; mean
> age, 67 +/- 1.5 yr) were compared with a group of samples from normal
> age-equivalent autopsied controls (n = 22; mean age, 68 +/- 2 yr) and
> autopsied AD brains (n = 11; mean age, 73 +/- 2 yr). Samples were
> assayed for choline acetyltransferase (ChAT), acetylcholinesterase,
> binding to [3H]quinuclidinyl benzilate as an index of total
> muscarinic cholinergic binding, and [3H]pirenzepine binding as an
> index of M1 cholinergic receptor subtype binding. Mean levels of ChAT
> activity were decreased in the biopsied patients to 36% of age-
> matched autopsied controls. The loss of ChAT activity correlated
> significantly with the Mini-Mental State Examination, an index of
> global cognitive function. Mean ChAT activity in autopsied AD cortex
> was further decreased compared with controls, indicating continuous
> decline through the course of the disease. Acetylcholinesterase
> followed a similar, less dramatic decline. No differences were found
> in [3H]quinuclidinyl benzilate binding or [3H]pirenzepine binding
> between biopsied and autopsied controls. Neuritic plaque counts did
> not correlate with either the Mini-Mental State Examination or ChAT
> activity in the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
> AD - Department of Psychiatry
> AD - University of Pittsburgh Medical Center
> AD - PA.
> SO - Ann Neurol 1992 Nov;32(5):625-32
> DP - 1992 Nov
> TA - Ann Neurol
> PG - 625-32
> IP - 5
> VI - 32
> IS - 0364-5134
> UI - 93080292
>> 14
> AU - McLachlan DR
> AU - Fraser PE
> AU - Dalton AJ
> TI - Aluminium and the pathogenesis of Alzheimer's disease: a summary of
> evidence.
> AB - Known risk factors for Alzheimer's disease (AD) are few and
> insufficient knowledge is available to recommend steps to reduce AD
> in our ageing populations. Although not 'the cause', considerable
> evidence implicates human ingestion of aluminium as a possible risk
> factor for the expression of dementia of the Alzheimer type. A recent
> epidemiological study in Ontario relating the incidence of AD to
> aluminium in drinking water strongly supports this conclusion. To
> test further the hypothesis that aluminium may play a role in the
> pathogenesis of AD we conducted a clinical trial employing the
> trivalent metal ion binding compound, desferrioxamine. The design was
> a two-year randomized trial with behavioural assessments blinded to
> study assignment. Sixty-three patients with probable AD were selected
> who were living at home and were under 74 years. Forty-eight signed
> an informed consent and completed all initial testing. The main
> outcome measure was a video-recorded home-behavioural assessment of
> measures of skills of daily living. The principal outcome was that
> the mean slope for performance of the skills of daily living for the
> group without treatment was -1.72% maximum score/month, compared to -
> 0.87% maximum score/month for the group treated with desferrioxamine
> (P = 0.038). Considerable evidence supports the hypothesis that
> aluminium has an active role in the pathogenesis of AD.
> AD - Centre for Research in Neurodegenerative Diseases
> AD - University of Toronto
> AD - Ontario
> AD - Canada.
> SO - Ciba Found Symp 1992;169:87-98; discussion 99-108
> DP - 1992
> TA - Ciba Found Symp
> PG - 87-98; discussion 99-108
> VI - 169
> IS - 0300-5208
> UI - 93145771
>> [this is a reference of negative-evidence?]
>> 15
> AU - Landsberg J
> AU - McDonald B
> AU - Grime G
> AU - Watt F
> TI - Microanalysis of senile plaques using nuclear microscopy.
> AB - Silver-staining "senile" plaques occurring in the brain are a major
> part of the pathology of Alzheimer's disease. The elemental
> composition of these structures, and the possible presence of
> aluminum and silicon in these structures, has been the subject of an
> increasing research effort over the last decade. However, the results
> have often been contradictory. Using a scanning proton microprobe,
> the elemental composition of senile plaques has been determined. This
> instrument, similar to an electron probe, uses a focused beam of
> protons scanned across a sample to map the elements. The technique is
> absolutely quantitative and is sensitive down to the parts per
> million level. Tissue from six cases of clinically and pathologically
> characterized cases of Alzheimer's disease and two aged
> neurologically normal controls was scanned. It was found that
> aluminum and silicon occur at a level of 50 ppm or greater in the
> cores of 20% of senile plaques and that the total occurrence of
> aluminum or silicon in scans containing plaques was not above
> background. The major uncertainties affecting interpretation of
> results of this kind are discussed, and it is suggested that the
> least controllable factor is contamination in the reagents used to
> prepare and stain the tissue. This indicates that until plaques can
> be unambiguously identified and analyzed in untreated tissue, no
> conclusion can be reached on whether senile plaques contain aluminum
> and silicon.
> AD - SPM Unit Particle and Nuclear Physics Laboratory
> AD - Oxford
> AD - UK.
> SO - J Geriatr Psychiatry Neurol 1993 Apr-Jun;6(2):97-104
> DP - 1993 Apr-Jun
> TA - J Geriatr Psychiatry Neurol
> PG - 97-104
> IP - 2
> VI - 6
> IS - 0891-9887
> UI - 93290761
>>>>>> >Ivan Reid, Paul Scherrer Institute, CH. reid at cvax.psi.ch>
