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

Autor:	Wijesinghe P; 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., Shankar SK; Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India., Yasha TC; Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India., Gorrie C; School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, Australia., Amaratunga D; Nonclinical Biostatistics, anssen Research & Development, Raritan, NJ, USA., Hulathduwa S; Department of Forensic Medicine, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka., Kumara KS; Department of Judicial Medical Office, Colombo South Teaching Hospital, Colombo, Sri Lanka., Samarasinghe K; Department of Pathology, University of Srijayewardenepura, Nugegoda, Sri Lanka., Suh YH; Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea.; NRI, Gachon University, Incheon, South Korea., Steinbusch HW; Department of Translational Neuroscience, Faculty Health, Medicine & Life Sciences, Maastricht University, Maastricht, Netherlands., De Silva KR; 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.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2016 Oct 18; Vol. 54 (4), pp. 1607-1618.
DOI:	10.3233/JAD-160425
Abstrakt:	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.
Databáze:	MEDLINE
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