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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease

The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10-25). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.
1552-5260
1407-1416
Lill, Christina M.
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Lill, Christina M., Rengmark, Aina, Pihlstrøm, Lasse, Fogh, Isabella, Shatunov, Aleksey, Sleiman, Patrick M., Wang, Li-San, Liu, Tian, Lassen, Christina F., Meissner, Esther, Alexopoulos, Panos, Calvo, Andrea, Chio, Adriano, Dizdar, Nil, Faltraco, Frank, Forsgren, Lars, Kirchheiner, Julia, Kurz, Alexander, Larsen, Jan P., Liebsch, Maria, Linder, Jan, Morrison, Karen E., Nissbrandt, Hans, Otto, Markus, Pahnke, Jens, Partch, Amanda, Restagno, Gabriella, Rujescu, Dan, Schnack, Cathrin, Shaw, Christopher E., Shaw, Pamela J., Tumani, Hayrettin, Tysnes, Ole-Bjørn, Valladares, Otto, Silani, Vincenzo, van den Berg, Leonard H., van Rheenen, Wouter, Veldink, Jan H., Lindenberger, Ulman, Steinhagen-Thiessen, Elisabeth, Teipel, Stefan, Perneczky, Robert, Hakonarson, Hakon, Hampel, Harald, von Arnim, Christine A.F., Olsen, Jørgen H., Van Deerlin, Vivianna M., Al-Chalabi, Ammar, Toft, Mathias, Ritz, Beate and Bertram, Lars (2015) The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimer's & Dementia, 11 (12), 1407-1416. (doi:10.1016/j.jalz.2014.12.009). (PMID:25936935)

Record type: Article

Abstract

A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10-25). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.

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e-pub ahead of print date: 30 April 2015
Published date: December 2015
Organisations: Medical Education

Identifiers

Local EPrints ID: 398180
URI: http://eprints.soton.ac.uk/id/eprint/398180
ISSN: 1552-5260
PURE UUID: 187df3b9-701d-4c34-b5ce-43273dd35d22
ORCID for Karen E. Morrison: ORCID iD orcid.org/0000-0003-0216-5717

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Date deposited: 20 Jul 2016 13:24
Last modified: 17 Dec 2019 01:32

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Contributors

Author: Christina M. Lill
Author: Aina Rengmark
Author: Lasse Pihlstrøm
Author: Isabella Fogh
Author: Aleksey Shatunov
Author: Patrick M. Sleiman
Author: Li-San Wang
Author: Tian Liu
Author: Christina F. Lassen
Author: Esther Meissner
Author: Panos Alexopoulos
Author: Andrea Calvo
Author: Adriano Chio
Author: Nil Dizdar
Author: Frank Faltraco
Author: Lars Forsgren
Author: Julia Kirchheiner
Author: Alexander Kurz
Author: Jan P. Larsen
Author: Maria Liebsch
Author: Jan Linder
Author: Hans Nissbrandt
Author: Markus Otto
Author: Jens Pahnke
Author: Amanda Partch
Author: Gabriella Restagno
Author: Dan Rujescu
Author: Cathrin Schnack
Author: Christopher E. Shaw
Author: Pamela J. Shaw
Author: Hayrettin Tumani
Author: Ole-Bjørn Tysnes
Author: Otto Valladares
Author: Vincenzo Silani
Author: Leonard H. van den Berg
Author: Wouter van Rheenen
Author: Jan H. Veldink
Author: Ulman Lindenberger
Author: Elisabeth Steinhagen-Thiessen
Author: Stefan Teipel
Author: Robert Perneczky
Author: Hakon Hakonarson
Author: Harald Hampel
Author: Christine A.F. von Arnim
Author: Jørgen H. Olsen
Author: Vivianna M. Van Deerlin
Author: Ammar Al-Chalabi
Author: Mathias Toft
Author: Beate Ritz
Author: Lars Bertram

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