Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls.
Occurrence of amyloid beta (Abeta) dense-core plaques in the brain is one of the chief hallmarks of Alzheimer's disease (AD). It is not yet clear what factors are responsible for the aggregation of Abeta in the formation of these plaques. Using Tg2576 and PSAPP mouse models that exhibit age-related development of amyloid plaques similar to that observed in AD, we showed that approximately 95% of dense plaques in Tg2576 and approximately 85% in PSAPP mice are centered on vessel walls or in the immediate perivascular regions. Stereoscopy and simulation studies focusing on smaller plaques suggested that vascular associations for both Tg2576 and PSAPP mice were dramatically higher than those encountered by chance alone. We further identified ultrastructural microvascular abnormalities occurring in association with dense plaques. Although occurrence of gross cerebral hemorrhage was infrequent, we identified considerable infiltration of the serum proteins immunoglobulin and albumin in association with dense plaques. Together with earlier evidence of vascular clearance of Abeta, our data suggest that perturbed vascular transport and/or perivascular enrichment of Abeta leads to the formation of vasocentric dense plaques in Tg2576 and PSAPP mouse models of AD.
Kumar-Singh
Samir
S
Department of Molecular Genetics VIB8, Neurodegenerative Brain Diseases Research Group, Molecular Neuropathology Project, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. samir.kumarsingh@ua.ac.be
Pirici
Daniel
D
McGowan
Eileen
E
Serneels
Sally
S
Ceuterick
Chantal
C
Hardy
John
J
Duff
Karen
K
Dickson
Dennis
D
Van Broeckhoven
Christine
C
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1; D012709:Serum Albumin
D016564:Amyloid beta-Protein Precursor; D007136:Immunoglobulins; D008565:Membrane Proteins; D053764:Presenilin-1; D012709:Serum Albumin