Cerebral amyloid angiopathy: Accumulation of Aβ in interstitial fluid drainage pathways in Alzheimer's disease

Roy O. Weller, Adrian Massey, Yu-Min Kuo, Alex E. Roher

研究成果: Article同行評審

106 引文 斯高帕斯(Scopus)

摘要

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) peptides in the walls of arteries both in the cortex and meninges. Here, we test the hypothesis that CAA results from the progressive accumulation of Aβ in the perivascular interstitial fluid drainage pathways of the brain. Experimental studies have shown that interstitial fluid (ISF) from the rat brain flows along periarterial spaces to join the cerebrospinal fluid (CSF) to drain to cervical lymph nodes. Such lymphatic drainage plays a key role in B-cell and T-cell mediated immunity of the brain. Anatomical studies have defined periarterial ISF drainage pathways in the human brain that are homologous with the lymphatic pathways in the rat brain but are largely separate from the CSF. Periarterial channels in the brain in man are in continuity with those of leptomeningeal arteries and can be traced from the brain to the extracranial portions of the internal carotid arteries related to deep cervical lymph nodes. The pattern of deposition of Aβ in senile plaques and in CAA suggests that Aβ accumulates in pericapillary and periarterial ISF drainage pathways. Aβ could accumulate in CAA due to either (i) increased production of Aβ, (ii) reduced solubility of Aβ peptides, or (iii) impedance of drainage of Aβ along periarterial ISF drainage pathways within the brain and leptomeninges due to aging factors in cerebral arteries. Elucidation of factors that reduce elimination of Aβ via perivascular drainage pathways may lead to their rectification and to new strategies for treatment of Alzheimer's disease.

原文English
頁(從 - 到)110-117
頁數8
期刊Annals of the New York Academy of Sciences
903
DOIs
出版狀態Published - 2000 一月 1

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)
  • 科學史與哲學

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