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

Article type: Research Article

Authors: Wijesinghe, Printha^a | Shankar, S.K.^b | Yasha, T.C.^b | Gorrie, Catherine^c | Amaratunga, Dhammika^d | Hulathduwa, Sanjayah^e | Kumara, K. Sunil^f | Samarasinghe, Kamani^g | Suh, Yoo-hun^{h; i} | Steinbusch, Harry W.M.^j | De Silva, K. Ranil D.^{a; *}

Affiliations: [a] 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 | [b] Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India | [c] School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, Australia | [d] Nonclinical Biostatistics, anssen Research & Development, Raritan, NJ, USA | [e] Department of Forensic Medicine, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka | [f] Department of Judicial Medical Office, Colombo South Teaching Hospital, Colombo, Sri Lanka | [g] Department of Pathology, University of Srijayewardenepura, Nugegoda, Sri Lanka | [h] Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea | [i] NRI, Gachon University, Incheon, South Korea | [j] Department of Translational Neuroscience, Faculty Health, Medicine & Life Sciences, Maastricht University, Maastricht, Netherlands

Correspondence: [*] Correspondence to: Prof. K. Ranil D. De Silva, Interdisciplinary Center for Innovation in Biotechnology & Neuroscience, Genetic Diagnostic and Research Laboratory, Department of Anatomy, Faculty of Medical Sciences, University ofSrijayewardenepura, 10250 Nugegoda, Sri Lanka. Tel.: +94112802164; Mobile: +94777423197; Fax: +94 112801480; E-mail: [email protected]; [email protected].

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.

Keywords: Alzheimer’s disease, apolipoprotein E, atherosclerosis, cerebral small vessel diseases, neuropathology

DOI: 10.3233/JAD-160425

Journal: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1607-1618, 2016