Amyloid beta-protein (A beta) accumulation in the leptomeninges during aging and in Alzheimer disease.
The results of well-characterized two-site enzyme immunoassays showed that the crude leptomeninges (consisting of the pia matter, arachnoid matter, and leptomeningeal vessels [LV]) from aged control brains and brains affected by Alzheimer disease (AD) contain very high levels of amyloid beta-protein (A beta). To learn about the source of A beta, we carefully dissected out both leptomeninges (LM) and LV under a dissecting microscope and determined the levels of soluble A beta in each. The purity of these dissected tissues was confirmed by the absence or presence of alpha-smooth muscle actin representing LV by Western blotting. Surprisingly, the amounts of A beta in each dissected sample were nearly equivalent on a weight basis. In each compartment from aged controls the level of A beta 1-42 was comparable to that of A beta 1-40, while in AD brain A beta 1-40 was a predominant species in both LM and LV. In some cases careful immunocytochemical examination revealed the presence of A beta deposits that were immunolabeled by several A beta monoclonal antibodies in leptomeningeal layers (most often in the arachnoid matter). The extent of A beta deposition in LM appeared to be much less than that explained by the soluble A beta levels, suggesting that immunocytochemically undetectable A beta can accumulate in LM. These observations indicate that leptomeninges are a large reservoir of A beta in normal aged individuals and in AD patients.
Hamano
T
T
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
Yoshimura
M
M
Yamazaki
T
T
Shinkai
Y
Y
Yanagisawa
K
K
Kuriyama
M
M
Ihara
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001099:Arachnoid / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010841:Pia Mater / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D012995:Solubility
D016229:Amyloid beta-Peptides