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Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease

Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease
Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease
Cerebral amyloid angiopathy in Alzheimer's disease is characterized by deposition of amyloid beta (Abeta) in cortical and leptomeningeal vessel walls. Although it has been suggested that Abeta is derived from vascular smooth muscle, deposition of Abeta is not seen in larger cerebral vessel walls nor in extracranial vessels. In the present study, we examine evidence for the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain in Alzheimer's disease and that this contributes significantly to cerebral amyloid angiopathy. There is firm evidence in animals for drainage of interstitial fluid from the brain to cervical lymph nodes along periarterial spaces; similar periarterial channels exist in humans. Biochemical study of 6 brains without Alzheimer's disease revealed a pool of soluble Abeta in the cortex. Histology and immunocytochemistry of 17 brains with Alzheimer's disease showed that Abeta accumulates five times more frequently around arteries than around veins, with selective involvement of smaller arteries. Initial deposits of Abeta occur at the periphery of arteries at the site of the putative interstitial fluid drainage pathways. These observations support the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain and contributes significantly to cerebral amyloid angiopathy in Alzheimer's disease.
0002-9440
725-733
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Massey, Adrian
d76d9923-e243-4b3d-9059-817e79a47e3f
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Hutchings, Margaret
44c5dfea-fefb-4f6e-91ff-0107896f13d1
Kuo, Yu-Min
899aea0a-6b3e-4eaf-8387-0f17746ef4d6
Roher, Alex E.
55dcb688-2a4c-44b3-adc3-f7e4982a7659
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Massey, Adrian
d76d9923-e243-4b3d-9059-817e79a47e3f
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Hutchings, Margaret
44c5dfea-fefb-4f6e-91ff-0107896f13d1
Kuo, Yu-Min
899aea0a-6b3e-4eaf-8387-0f17746ef4d6
Roher, Alex E.
55dcb688-2a4c-44b3-adc3-f7e4982a7659

Weller, Roy O., Massey, Adrian, Newman, Tracey A., Hutchings, Margaret, Kuo, Yu-Min and Roher, Alex E. (1998) Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. The American Journal of Pathology, 153 (3), 725-733.

Record type: Article

Abstract

Cerebral amyloid angiopathy in Alzheimer's disease is characterized by deposition of amyloid beta (Abeta) in cortical and leptomeningeal vessel walls. Although it has been suggested that Abeta is derived from vascular smooth muscle, deposition of Abeta is not seen in larger cerebral vessel walls nor in extracranial vessels. In the present study, we examine evidence for the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain in Alzheimer's disease and that this contributes significantly to cerebral amyloid angiopathy. There is firm evidence in animals for drainage of interstitial fluid from the brain to cervical lymph nodes along periarterial spaces; similar periarterial channels exist in humans. Biochemical study of 6 brains without Alzheimer's disease revealed a pool of soluble Abeta in the cortex. Histology and immunocytochemistry of 17 brains with Alzheimer's disease showed that Abeta accumulates five times more frequently around arteries than around veins, with selective involvement of smaller arteries. Initial deposits of Abeta occur at the periphery of arteries at the site of the putative interstitial fluid drainage pathways. These observations support the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain and contributes significantly to cerebral amyloid angiopathy in Alzheimer's disease.

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Published date: September 1998

Identifiers

Local EPrints ID: 73390
URI: http://eprints.soton.ac.uk/id/eprint/73390
ISSN: 0002-9440
PURE UUID: f3b5938c-01b4-417d-8ad3-9065db39f9ec
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

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Date deposited: 09 Mar 2010
Last modified: 28 Apr 2022 01:40

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Contributors

Author: Roy O. Weller
Author: Adrian Massey
Author: Margaret Hutchings
Author: Yu-Min Kuo
Author: Alex E. Roher

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