Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population

Wijesinghe, P; Shankar, SK; Yasha, TC; Gorrie, C; Amaratunga, D; Hulathduwa, S; Kumara, KS; Samarasinghe, K; Suh, YH; Steinbusch, HWM; De Silva, KRD

Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population

Wijesinghe, P Shankar, SK Yasha, TC Gorrie, C

Amaratunga, D Hulathduwa, S Kumara, KS Samarasinghe, K Suh, YH Steinbusch, HWM De Silva, KRD

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Publication Type:: Journal Article
Citation:: Journal of Alzheimer's Disease, 2016, 54 (4), pp. 1607 - 1618
Issue Date:: 2016-10-18

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Field	Value	Language
dc.contributor.author	Wijesinghe, P	en_US
dc.contributor.author	Shankar, SK	en_US
dc.contributor.author	Yasha, TC	en_US
dc.contributor.author	Gorrie, C https://orcid.org/0000-0001-5934-2492	en_US
dc.contributor.author	Amaratunga, D	en_US
dc.contributor.author	Hulathduwa, S	en_US
dc.contributor.author	Kumara, KS	en_US
dc.contributor.author	Samarasinghe, K	en_US
dc.contributor.author	Suh, YH	en_US
dc.contributor.author	Steinbusch, HWM	en_US
dc.contributor.author	De Silva, KRD	en_US
dc.date.issued	2016-10-18	en_US
dc.identifier.citation	Journal of Alzheimer's Disease, 2016, 54 (4), pp. 1607 - 1618	en_US
dc.identifier.issn	1387-2877	en_US
dc.identifier.uri	http://hdl.handle.net/10453/98898
dc.description.abstract	© 2016 - IOS Press and the authors. All rights reserved. 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 ϵ4 allele was significantly and strongly associated with Thal amyloid-β 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.	en_US
dc.relation.ispartof	Journal of Alzheimer's Disease	en_US
dc.relation.isbasedon	10.3233/JAD-160425	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Circle of Willis	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Cerebrovascular Disorders	en_US
dc.subject.mesh	Intracranial Arteriosclerosis	en_US
dc.subject.mesh	Alzheimer Disease	en_US
dc.subject.mesh	Methylenetetrahydrofolate Reductase (NADPH2)	en_US
dc.subject.mesh	Apolipoproteins E	en_US
dc.subject.mesh	Autopsy	en_US
dc.subject.mesh	Population Surveillance	en_US
dc.subject.mesh	Aging	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Sri Lanka	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.title	Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	54	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1702 Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	54	en_US

Abstract:

© 2016 - IOS Press and the authors. All rights reserved. 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 ϵ4 allele was significantly and strongly associated with Thal amyloid-β 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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http://hdl.handle.net/10453/98898