Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population
- Authors
- Wijesinghe, Printha; Shankar, S. K.; Yasha, T. C.; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K. Sunil; Samarasinghe, Kamani; Suh, Yoo-hun; Steinbusch, Harry W. M.; De Silva, K. Ranil D.
- Issue Date
- 2016
- Publisher
- IOS PRESS
- Keywords
- Alzheimer' s disease; apolipoprotein E; atherosclerosis; cerebral small vessel diseases; neuropathology
- Citation
- JOURNAL OF ALZHEIMERS DISEASE, v.54, no.4, pp.1607 - 1618
- Journal Title
- JOURNAL OF ALZHEIMERS DISEASE
- Volume
- 54
- Number
- 4
- Start Page
- 1607
- End Page
- 1618
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/9667
- DOI
- 10.3233/JAD-160425
- ISSN
- 1387-2877
- Abstract
- Background: Evidence from various consortia on vascular contributions has been inconsistent in determining the etiology of sporadic Alzheimer's disease (AD). Objective: To investigate vascular risk factors and cerebrovascular pathologies associated in manifestation of AD-related neuropathological changes of an elderly population. Methods: Postmortem brain samples from 76 elderly subjects (>= 50 years) were used to study genetic polymorphisms, intracranial atherosclerosis of the circle of Willis (IASCW), and microscopic infarcts in deep white matters. From this cohort, 50 brains (>= 60 years) were subjected to neuropathological diagnosis using immunohistopathological techniques. Results: Besides the association with age, the apolipoprotein E epsilon 4 allele was significantly and strongly associated with Thal amyloid-beta phases >= 1 [odds ratio (OR) = 6.76, 95% confidence interval (CI) 1.37-33.45] and inversely with Braak neurofibrillary tangle (NFT) stages >= III (0.02, 0.0-0.47). Illiterates showed a significant positive association for Braak NFT stages >= IV (14.62, 1.21-176.73) and a significant negative association for microscopic infarcts (0.15, 0.03-0.71) in deep white matters. With respect to cerebrovascular pathologies, cerebral small vessel lesions (white matter hyperintensities and cerebral amyloid angiopathy) showed a higher degree of associations among them and with AD-related neuropathological changes (p < 0.05) compared to large vessel pathology (IASCW), which showed a significant association only with Braak NFT stages >= I (p = 0.050). Conclusion: These findings suggest that besides age, education, and genetic factors, other vascular risk factors were not associated with AD-related neuropathological changes and urge prompt actions be taken against cerebral small vessel diseases since evidence for effective prevention is still lacking.
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