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Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease

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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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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  • DOI: https://doi.org/10.1007/s00401-008-0366-2

Keywords

  • Alzheimer’s disease
  • Cerebral amyloid angiopathy
  • Amyloid β-protein
  • Cerebral blood flow
  • Drainage