title: Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population.
abstract: Evidence from various consortia on vascular contributions has been inconsistent in determining the etiology of sporadic Alzheimer's disease (AD).
  
  
  
  To investigate vascular risk factors and cerebrovascular pathologies associated in manifestation of AD-related neuropathological changes of an elderly population.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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: 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.
authors: Printha
authors: P
authors: Wijesinghe
authors: Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India.
authors: S K
authors: SK
authors: Shankar
authors: Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore, India.
authors: T C
authors: TC
authors: Yasha
authors: School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, Australia.
authors: Catherine
authors: C
authors: Gorrie
authors: Nonclinical Biostatistics, anssen Research & Development, Raritan, NJ, USA.
authors: Dhammika
authors: D
authors: Amaratunga
authors: Department of Forensic Medicine, Faculty of Medical Sciences, University of Srijayewardenepura, Nugegoda, Sri Lanka.
authors: Sanjayah
authors: S
authors: Hulathduwa
authors: Department of Judicial Medical Office, Colombo South Teaching Hospital, Colombo, Sri Lanka.
authors: K Sunil
authors: KS
authors: Kumara
authors: Department of Pathology, University of Srijayewardenepura, Nugegoda, Sri Lanka.
authors: Kamani
authors: K
authors: Samarasinghe
authors: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea.|NRI, Gachon University, Incheon, South Korea.
authors: Yoo-Hun
authors: YH
authors: Suh
authors: Department of Translational Neuroscience, Faculty Health, Medicine & Life Sciences, Maastricht University, Maastricht, Netherlands.
authors: Harry W M
authors: HW
authors: Steinbusch
authors: 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.
authors: K Ranil D
authors: KR
authors: De Silva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology*; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001344:Autopsy; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D002941:Circle of Willis / Q000473:pathology; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D013188:Sri Lanka / Q000453:epidemiology
chemical_list: D001057:Apolipoproteins E; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Alzheimer’s disease; apolipoprotein E; atherosclerosis; cerebral small vessel diseases; neuropathology