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Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease

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Abstract

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of the amyloid β-protein (Aβ) within cerebral vessels. The involvement of different brain areas in CAA follows a hierarchical sequence similar to that of Alzheimer-related senile plaques. Alzheimer’s disease patients frequently exhibit CAA. The expansion of CAA in AD often shows the pattern of full-blown CAA. The deposition of Aβ within capillaries distinguishes two types of CAA. One with capillary Aβ-deposition is characterized by a strong association with the apolipoprotein E (APOE) ε4 allele and by its frequent occurrence in Alzheimer’s disease cases whereas the other one lacking capillary Aβ-deposits is not associated with APOE ε4. Capillary CAA can be seen in every stage of CAA or AD-related Aβ-deposition. AD cases with capillary CAA show more widespread capillary Aβ-deposition than non-demented cases as well as capillary occlusion. In a mouse model of CAA, capillary CAA was associated with capillary occlusion and cerebral blood flow disturbances. Thus, blood flow alterations with subsequent hypoperfusion induced by CAA-related capillary occlusion presumably point to a second mechanism in which Aβ adversely affects the brain in AD in addition to its direct neurotoxic effects.

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Acknowledgments

The work reviewed here was supported by the DFG: TH624/4-1 (DRT), TH624/4-2 (DRT), GH 12/2-1 (EG), GH 12/2-2 (EG); BONFOR: O-154.0041 (DRT), and the NIH-NIA: AG12411 (WSTG). The authors gratefully acknowledge I. Szász and H. U. Klatt for graphics and artwork. We thank Dr. A. Scheuerle for reading the manuscript.

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  1. Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Albert-Einstein-Allee 7, 89081, Ulm, Germany

    Dietmar Rudolf Thal

  2. Donald W. Reynolds Center on Aging, UAMS, Geriatric Research Education and Clinical Center, Veterans’ Affairs Medical Center, Little Rock, AR, USA

    W. Sue T. Griffin

  3. Laboratorium Pathologie Oost Nederland, Enschede, The Netherlands

    Rob A. I. de Vos

  4. Institute for Clinical Neuroanatomy, J. W. Goethe University, 60590, Frankfurt am Main, Germany

    Estifanos Ghebremedhin

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  1. Dietmar Rudolf Thal
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  4. Estifanos Ghebremedhin
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Correspondence to Dietmar Rudolf Thal.

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Thal, D.R., Griffin, W.S.T., de Vos, R.A.I. et al. Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease. Acta Neuropathol 115, 599–609 (2008). https://doi.org/10.1007/s00401-008-0366-2

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