An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology

Christian Wider, Owen A. Ross, Kenya Nishioka, Michael G. Heckman, Carles Vilariño-Güell, Barbara Jasinska-Myga, Nilufer Erketin-Taner, Rosa Rademakers, Neill R. Graff-Radford, Deborah C Mash, Spiridon Papapetropoulos, Ranjan Duara, Hirotake Uchikado, Zbigniew K. Wszolek, Matthew J. Farrer, Dennis W. Dickson

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Abstract

Purpose: The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies. Methods: A multicentre autopsy series (762 brain samples) with AD, LB or vascular pathology was examined. The effects of the tau gene (MAPT) H1 haplotype, the H1 specific SNP rs242557, APOE and the a-synuclein gene (SNCA) 3′UTR SNP rs356165 on the burden of AD and LB pathology were assessed. Neurofibrillary tangles (NFTs) were counted in four brain regions, senile plaques in five and LBs in four. Braak NFT stage, brain weight and presence of vascular pathology were also documented. Results: MAPT H1 associated with lower counts of NFTs in the middle frontal (p<0.001) and inferior parietal (p=0.005) cortices, and also with lower counts of senile plaques in the motor cortex (p=0.001). Associations of MAPT H1 with increased LB counts in the middle frontal cortex (p=0.011) and inferior parietal cortex (p=0.033) were observed but were not significant after multiple testing adjustment. The APOE 34 allele was strongly associated with overall Alzheimer type pathology (all p≤0.001). SNCA rs356165 and the MAPT H1 specific SNP rs242557 did not associate with AD or LB pathology. Conclusion: This study shows for the first time that MAPT H1 is associated with reduced Alzheimer type pathology which could have important implications for the understanding of disease mechanisms and their genetic determinants.

Original languageEnglish
Pages (from-to)424-429
Number of pages6
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume83
Issue number4
DOIs
StatePublished - Apr 1 2012

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Lewy Bodies
Pathology
Neurofibrillary Tangles
Alzheimer Disease
Single Nucleotide Polymorphism
Lewy Body Disease
Amyloid Plaques
Blood Vessels
Brain
Synucleins
Social Adjustment
Parietal Lobe
Motor Cortex
Frontal Lobe
Evaluation
Burden
Alzheimer
Haplotypes
Genes
Parkinson Disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

Cite this

Wider, C., Ross, O. A., Nishioka, K., Heckman, M. G., Vilariño-Güell, C., Jasinska-Myga, B., ... Dickson, D. W. (2012). An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology. Journal of Neurology, Neurosurgery and Psychiatry, 83(4), 424-429. https://doi.org/10.1136/jnnp-2011-301413

An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology. / Wider, Christian; Ross, Owen A.; Nishioka, Kenya; Heckman, Michael G.; Vilariño-Güell, Carles; Jasinska-Myga, Barbara; Erketin-Taner, Nilufer; Rademakers, Rosa; Graff-Radford, Neill R.; Mash, Deborah C; Papapetropoulos, Spiridon; Duara, Ranjan; Uchikado, Hirotake; Wszolek, Zbigniew K.; Farrer, Matthew J.; Dickson, Dennis W.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 83, No. 4, 01.04.2012, p. 424-429.

Research output: Contribution to journalArticle

Wider, C, Ross, OA, Nishioka, K, Heckman, MG, Vilariño-Güell, C, Jasinska-Myga, B, Erketin-Taner, N, Rademakers, R, Graff-Radford, NR, Mash, DC, Papapetropoulos, S, Duara, R, Uchikado, H, Wszolek, ZK, Farrer, MJ & Dickson, DW 2012, 'An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology', Journal of Neurology, Neurosurgery and Psychiatry, vol. 83, no. 4, pp. 424-429. https://doi.org/10.1136/jnnp-2011-301413
Wider, Christian ; Ross, Owen A. ; Nishioka, Kenya ; Heckman, Michael G. ; Vilariño-Güell, Carles ; Jasinska-Myga, Barbara ; Erketin-Taner, Nilufer ; Rademakers, Rosa ; Graff-Radford, Neill R. ; Mash, Deborah C ; Papapetropoulos, Spiridon ; Duara, Ranjan ; Uchikado, Hirotake ; Wszolek, Zbigniew K. ; Farrer, Matthew J. ; Dickson, Dennis W. / An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology. In: Journal of Neurology, Neurosurgery and Psychiatry. 2012 ; Vol. 83, No. 4. pp. 424-429.
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AU - Jasinska-Myga, Barbara

AU - Erketin-Taner, Nilufer

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