Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein.
We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and beta/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. beta/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.
Harrington
C R
CR
Department of Psychiatry, University of Cambridge, UK.
Perry
R H
RH
Perry
E K
EK
Hurt
J
J
McKeith
I G
IG
Roth
M
M
Wischik
C M
CM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006179:Gyrus Cinguli / Q000737:chemistry; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D016253:Microscopy, Immunoelectron; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D009778:Occipital Lobe / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016875:tau Proteins / Q000737:chemistry*
D016875:tau Proteins