Neuropathological and genetic determinants of dementia : a prospective and population-based study on very elderly finns

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The number of individuals suffering from dementia increases as the population ages. Alzheimer’s disease (AD) is the most common type of dementia, neuropathologically characterized by neuritic plaques (NP) and neurofibrillary tangles (NFT). Cerebral amyloid angiopathy (CAA, deposition of amyloid β (Aβ) in the cerebral vessels) is often found in AD, but its role in dementia has been unclear. Recent genome-wide association studies have revealed approximately 30 AD risk loci. The aim of this thesis was to assess the neuropathological and genetic risk factors of dementia in a population-based cohort of very elderly (Vantaa 85+). Of the 601 subjects aged >85 years and living in Vantaa in 1991, 300 (mean age‐at‐death 92±3.7 years) were examined neuropathologically and 278 genetically. The diagnosis of clinical dementia was based on the DSM III-R criteria. In addition to AD –related neuropathology, Lewy body (LB)-related pathology and several vascular pathologies were analysed. Genetic analyses were based on genome wide approaches. 65% of the study subjects were demented. Except for one subject, at least one type of neuropathology was found in every individual. Presence of at least two of these pathologies almost doubled the risk of dementia. Severe NFT -pathology was the most common finding, and associated most strongly with dementia. LB-related pathology and small cortical infarcts in the anterior brain regions were also independent contributors of dementia. In addition, severe CAA in the frontal lobe was nearly significantly associated with dementia. CAA was found in nearly 70% of the subjects, but it was mostly mild, found approximately in 1% of the brain vessels. The parietal and frontal lobes were affected most often. In this study, the presence of capillary Aβ (capAβ) was for the first time investigated in a population-based setting and was found in 28.6% of the subjects. Interestingly, every subject with severe capAβ deposition in multiple brain areas was demented. Analyses of 24 of previously known genetic risk loci for AD revealed associations with various types of AD neuropathologies (NP, NFT, CAA, capAβ). Genetic risk factors for capAβ were identified for the first time. This study confirmed in a population-based setting previously described findings on neuropathological and genetic factors of dementia. The very high frequency of CAA and the association of capAβ with dementia were shown. Genetic associations of capAβ were reported for the first time. Key words: dementia, Alzheimer´s disease, cerebral amyloid angiopathy, capillary amyloid angiopathy, population-based study
  • Tanskanen, Maarit, Handledare
  • Myllykangas, Liisa, Handledare
  • Paetau, Anders, Handledare
Tryckta ISBN978-951-51-4472-0
Elektroniska ISBN978-951-51-4473-7
StatusPublicerad - 2018
MoE-publikationstypG5 Doktorsavhandling (artikel)

Bibliografisk information

M1 - 122 s. + liitteet


  • 3112 Neurovetenskaper
  • 3124 Neurologi och psykiatri
  • 3111 Biomedicinska vetenskaper

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