Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive impairment

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Kaivola , K , Jansson , L , Saarentaus , E , Kiviharju , A , Rantalainen , V , Eriksson , J G , Strandberg , T E , Polvikoski , T , Myllykangas , L & Tienari , P J 2018 , ' Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive impairment ' , Neurobiology of Aging , vol. 64 , ARTN 159.e1 . https://doi.org/10.1016/j.neurobiolaging.2017.12.008

Title: Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive impairment
Author: Kaivola, Karri; Jansson, Lilja; Saarentaus, Elmo; Kiviharju, Anna; Rantalainen, Ville; Eriksson, Johan G.; Strandberg, Timo E.; Polvikoski, Tuomo; Myllykangas, Liisa; Tienari, Pentti J.
Contributor organization: Research Programs Unit
University of Helsinki
Research Programme for Molecular Neurology
Neurologian yksikkö
Department of Neurosciences
Department of Psychology and Logopedics
Department of General Practice and Primary Health Care
Johan Eriksson / Principal Investigator
Timo Strandberg / Principal Investigator
Department of Medicine
Department of Pathology
Pentti Tienari / Principal Investigator
HUS Internal Medicine and Rehabilitation
HUS Neurocenter
Developmental Psychology Research Group
Genomics of Neurological and Neuropsychiatric Disorders
Date: 2018-04
Language: eng
Number of pages: 4
Belongs to series: Neurobiology of Aging
ISSN: 0197-4580
DOI: https://doi.org/10.1016/j.neurobiolaging.2017.12.008
URI: http://hdl.handle.net/10138/300596
Abstract: Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease that resembles early-onset frontotemporal dementia with bone lesions called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with Alzheimer's disease when heterozygous. Here, we studied the PLOSLFIN TYROBP deletion that covers 4 of the gene's 5 exons. We genotyped 3220 older Finns (mean age 79, range 58-104) and found 11 deletion carriers (mean age 78, range 60-94). The carrier prevalence was 0.0034 (1 in 293) that matches previous findings in younger cohorts suggesting no significant early mortality. By comparing Mini-Mental State Examination (MMSE) scores and diagnoses of dementia, we did not find any significant differences between TYROBP deletion carriers and noncarriers (all p-values >0.5). Neuropathological analysis of 2 deletion carriers (aged 89 and 94 years) demonstrated only minimal beta amyloid pathology (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score 0). Collectively these results suggest that heterozygous carriership of the TYROBP deletion is not a major risk factor of cognitive impairment. (C) 2017 Elsevier Inc. All rights reserved.
Subject: Genetics
Alzheimer's disease
515 Psychology
3112 Neurosciences
3124 Neurology and psychiatry
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

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