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Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population.
J Alzheimers Dis 2016; 54(4):1607-1618JA

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 ɛ4 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.

Authors+Show Affiliations

Interdisciplinary Center for Innovation in Biotechnology & Neuroscience, Genetic Diagnostic and Research Laboratory, Department of Anatomy, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka.Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India.Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India.School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, Australia.Nonclinical Biostatistics, anssen Research & Development, Raritan, NJ, USA.Department of Forensic Medicine, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka.Department of Judicial Medical Office, Colombo South Teaching Hospital, Colombo, Sri Lanka.Department of Pathology, University of Srijayewardenepura, Nugegoda, Sri Lanka.Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea. NRI, Gachon University, Incheon, South Korea.Department of Translational Neuroscience, Faculty Health, Medicine & Life Sciences, Maastricht University, Maastricht, Netherlands.Interdisciplinary Center for Innovation in Biotechnology & Neuroscience, Genetic Diagnostic and Research Laboratory, Department of Anatomy, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27589527

Citation

Wijesinghe, Printha, et al. "Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence From a South Asian Aging Population." Journal of Alzheimer's Disease : JAD, vol. 54, no. 4, 2016, pp. 1607-1618.
Wijesinghe P, Shankar SK, Yasha TC, et al. Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population. J Alzheimers Dis. 2016;54(4):1607-1618.
Wijesinghe, P., Shankar, S. K., Yasha, T. C., Gorrie, C., Amaratunga, D., Hulathduwa, S., ... De Silva, K. R. (2016). Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population. Journal of Alzheimer's Disease : JAD, 54(4), pp. 1607-1618.
Wijesinghe P, et al. Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence From a South Asian Aging Population. J Alzheimers Dis. 2016 10 18;54(4):1607-1618. PubMed PMID: 27589527.
* Article titles in AMA citation format should be in sentence-case
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 - 2016/10/22/pubmed PY - 2018/1/25/medline PY - 2016/9/3/entrez KW - Alzheimer’s disease KW - apolipoprotein E KW - atherosclerosis KW - cerebral small vessel diseases KW - neuropathology SP - 1607 EP - 1618 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 54 IS - 4 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 ɛ4 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/27589527/Vascular_Contributions_in_Alzheimer's_Disease_Related_Neuropathological_Changes:_First_Autopsy_Evidence_from_a_South_Asian_Aging_Population_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-160425 DB - PRIME DP - Unbound Medicine ER -