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Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype.

Publication ,  Journal Article
Stopa, EG; Butala, P; Salloway, S; Johanson, CE; Gonzalez, L; Tavares, R; Hovanesian, V; Hulette, CM; Vitek, MP; Cohen, RA
Published in: Stroke
March 2008

BACKGROUND AND PURPOSE: We examined the associations among the vascular beta-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD). METHODS: Post-mortem pathology brain specimens from 76 patients with AD and 19 non-AD age control subjects were studied. We analyzed arterioles of the frontal cortex (Brodmann area 10) by immunohistochemistry and morphometry, and derived measures of vascular beta-amyloid level, smooth muscle actin (SMA) volume, and arteriolar wall thickness and lumen diameter. APOE genotype was determined for each case. RESULTS: Overall, there was a striking reciprocal relationship between arteriolar beta-amyloid volume and smooth muscle actin (P<0.0001). In addition, there was a strong positive association between progressively accumulating vascular beta-amyloid and augmentations in both wall thickness (P<0.0001) and lumen width (P<0.0001). In comparison with non-AD control subjects, smooth muscle actin was decreased in patients clinically diagnosed with AD and was reduced >10-fold in cases with AD pathology (Braak I to VI) compared with those lacking AD neuropathology. Significantly altered composition and structure of cortical vessels in pre-Braak stages corroborated our hypothesis that arterioles are devastated early in the AD pathological process. Smooth muscle actin, arteriolar wall thickness, and luminal diameter did not vary with Braak stage severity (P>0.05), indicating that substantial arteriolar damage may precede at least some of the interstitial plaques and neuronal tangles. Moreover, the structural and biochemical arteriolar abnormalities did not vary as a function of APOE genotype (P>0.05). CONCLUSIONS: We postulate that in elderly patients, the continually progressing beta-amyloid-associated angiopathy, at the arteriolar level, harms the contractile apparatus and cerebral blood flow autoregulation, thereby making the downstream capillaries vulnerable to damage. Collectively, our observations lend further support to the idea that microvascular damage has a role, perhaps relatively early, in the onset of major AD pathology.

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Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

March 2008

Volume

39

Issue

3

Start / End Page

814 / 821

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Neurology & Neurosurgery
  • Muscle, Smooth, Vascular
  • Male
  • Immunohistochemistry
  • Humans
  • Genotype
  • Frontal Lobe
  • Female
  • Cadaver
 

Citation

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Stopa, E. G., Butala, P., Salloway, S., Johanson, C. E., Gonzalez, L., Tavares, R., … Cohen, R. A. (2008). Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype. Stroke, 39(3), 814–821. https://doi.org/10.1161/STROKEAHA.107.493429
Stopa, Edward G., Parag Butala, Stephen Salloway, Conrad E. Johanson, Liliana Gonzalez, Rosemarie Tavares, Virginia Hovanesian, Christine M. Hulette, Michael P. Vitek, and Ronald A. Cohen. “Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype.Stroke 39, no. 3 (March 2008): 814–21. https://doi.org/10.1161/STROKEAHA.107.493429.
Stopa EG, Butala P, Salloway S, Johanson CE, Gonzalez L, Tavares R, et al. Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype. Stroke. 2008 Mar;39(3):814–21.
Stopa, Edward G., et al. “Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype.Stroke, vol. 39, no. 3, Mar. 2008, pp. 814–21. Pubmed, doi:10.1161/STROKEAHA.107.493429.
Stopa EG, Butala P, Salloway S, Johanson CE, Gonzalez L, Tavares R, Hovanesian V, Hulette CM, Vitek MP, Cohen RA. Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype. Stroke. 2008 Mar;39(3):814–821.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

March 2008

Volume

39

Issue

3

Start / End Page

814 / 821

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Neurology & Neurosurgery
  • Muscle, Smooth, Vascular
  • Male
  • Immunohistochemistry
  • Humans
  • Genotype
  • Frontal Lobe
  • Female
  • Cadaver