from Part two - Pathological issues
Published online by Cambridge University Press: 06 July 2010
Summary
Altered processing of tau protein is a characteristic feature of Alzheimer's disease (AD) that, unlike the accumulation of amyloid β-protein, is strongly correlated with clinical dementia. In AD, tau is substantially redistributed from its soluble, predominantly axonal form into insoluble PHF-tau that accumulates in the somatodendritic compartment. Although hyperphosphorylated tau also accumulates, this accounts for no more than 5% of the total PHF-tau during any stage of the development of AD. In contrast, cortical Lewy body dementia in the elderly is not associated with these changes in tau processing and such patients have less than one-tenth of the levels of both PHF-tau and neurofibrillary pathology as those found in AD. These findings support the notion that the pathobiology of these two disorders is distinct and provide the opportunity to compare non-PHF- with PHF-type dementias. Both these late-onset dementias are associated with comparable increases in the frequency of the apolipoprotein E (APO E) type ∈4 allele (in excess of 30%, as compared with 14% in controls and 10% in Parkinson's disease). The extent of abnormal PHF-tau levels in AD is unaffected by the presence of an e4 allele, suggesting that APO E polymorphisms do not directly influence the pathological processing of tau. These findings suggest that cortical Lewy body dementia has an aetiopathogenesis that is distinct from AD. Furthermore, APO E polymorphisms influence the development of dementia in both AD and cortical, but not subcortical Lewy body disease by mechanisms(s) that remain to be identified.
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