TY - JOUR
T1 - Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population
AU - Wijesinghe, Printha
AU - Shankar, S. K.
AU - Yasha, T. C.
AU - Gorrie, Catherine
AU - Amaratunga, Dhammika
AU - Hulathduwa, Sanjayah
AU - Kumara, K. Sunil
AU - Samarasinghe, Kamani
AU - Suh, Yoo-hun
AU - Steinbusch, Harry W. M.
AU - De Silva, K. Ranil D.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - apolipoprotein E
KW - atherosclerosis
KW - cerebral small vessel diseases
KW - neuropathology
U2 - 10.3233/JAD-160425
DO - 10.3233/JAD-160425
M3 - Article
SN - 1387-2877
VL - 54
SP - 1607
EP - 1618
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -