Deposition of beta-amyloid subtypes 40 and 42 differentiates dementia with Lewy bodies from Alzheimer disease.
BACKGROUND
Alterations in the metabolism of the amyloid precursor protein and the formation of beta-amyloid (Abeta) plaques are associated with neuronal death in Alzheimer disease (AD). The plaque subtype Abeta(x-42) occurs as an early event, with Abeta(x-40) plaques forming at a later stage. In dementia with Lewy bodies (DLB), an increase in the amount of cortical Abeta occurs without severe cortical neuronal losses.


OBJECTIVE
To advance our understanding of the natural history of Abeta in neurodegenerative diseases.


METHODS
We evaluated the expression of Abeta(x-40) and Abeta(x-42) in DLB using monoclonal antibodies and immunohistochemical techniques in 5 brain regions. The data were compared with those elicited with normal aging and from patients with AD.


METHODS
A postmortem study involving 19 patients with DLB without concurrent neuritic degeneration, 10 patients with AD, and 17 aged persons without dementia for control subjects.


RESULTS
The Abeta plaques were more numerous in patients with DLB than in controls in most brain regions, although the Abeta(x-42) plaque subtype was predominant in both conditions. Overall, Abeta(x-42) plaque density was similar in patients with DLB and those with AD, but Abeta(x-40) plaques were more numerous in persons with AD than in those with DLB. The ratio of Abeta(x-40) to Abeta(x-42) plaques was significantly reduced in persons with DLB compared with patients with AD.


CONCLUSIONS
The Abeta plaques were more numerous in patients with DLB than persons with normal aging, but the plaque subtypes were similar. The relative proportion of the 2 Abeta plaque subtypes in DLB is distinguishable from that in AD.
Lippa
C F
CF
Department of Neurology, MCP-Hahnemann University, Philadelphia, PA 19129, USA. lippa@auhs.edu
Ozawa
K
K
Mann
D M
DM
Ishii
K
K
Smith
T W
TW
Arawaka
S
S
Mori
H
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000911:Antibodies, Monoclonal; D001923:Brain Chemistry; D016022:Case-Control Studies; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000737:chemistry*; D008297:Male; D008875:Middle Aged
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal