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Relative paucity of tau accumulation in the small areas with abundant Aβ42-positive capillary amyloid angiopathy within a given cortical region in the brain of patients with Alzheimer pathology

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Abstract

Cerebral amyloid angiopathy (CAA) is a manifestation of amyloid β-protein (Aβ) accumulation in the elderly as well as in patients with Alzheimer’s disease (AD). Two types of CAA have been noted, based on the type of vasculature in which Aβ is deposited: cerebral capillary amyloid angiopathy (capCAA) and non-capCAA. Non-capCAA is a common form of CAA that consists of Aβ deposited in arteries and arterioles. Recent information on Aβ metabolism in the brain suggests that non-capCAA is associated with Aβ secretion into the cerebrospinal fluid via the perivascular space, whereas capCAA is associated with Aβ removal to blood plasma via the capillary endothelium. Aβ40, a major and relatively soluble Aβ isoform, is deposited predominantly in non-capCAA, and Aβ42, which is insoluble and associated more closely than Aβ40 with AD, is deposited predominantly in capCAA. Studying small areas of microscopic size within a given cortical region, we found an inverse association of capCAA and senile plaques. We also found a relative paucity of tau pathology in the small areas with abundant capCAA compared with the small areas with abundant senile plaques within a cortical region with the same cytoarchitecture. We suppose that both capCAA and senile plaques indicate high Aβ42 in the neuropil but that only Aβ42 in the form of insoluble deposits in senile plaques promotes tau abnormality.

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Acknowledgement

We thank Prof. Hiroshi Mori for providing antibodies to Aβ carboxyl terminals. This research was supported by grant in aid for scientific research from the ministry of education, culture, sports, science and technology (14570957).

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Authors and Affiliations

  1. Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-0057, Japan

    Kenichi Oshima & Kazuhiro Niizato

  2. Laboratory Medicine, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-0057, Japan

    Kuniaki Tsuchiya

  3. Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, 156-8585, Japan

    Haruhiko Akiyama, Hiromi Kondo, Chie Haga & Yoko Shimomura

  4. Department of Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan

    Eizo Iseki

  5. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA

    Hirotake Uchikado

  6. Soga Hospital, Odawara, Japan

    Masanori Kato

  7. Department of Psychiatry, Juntendo Medical University, Tokyo, Japan

    Heii Arai

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  1. Kenichi Oshima
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Correspondence to Haruhiko Akiyama.

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Oshima, K., Akiyama, H., Tsuchiya, K. et al. Relative paucity of tau accumulation in the small areas with abundant Aβ42-positive capillary amyloid angiopathy within a given cortical region in the brain of patients with Alzheimer pathology. Acta Neuropathol 111, 510–518 (2006). https://doi.org/10.1007/s00401-006-0070-z

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  • DOI: https://doi.org/10.1007/s00401-006-0070-z

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