title: MAPT H1 haplotype is associated with enhanced α-synuclein deposition in dementia with Lewy bodies.
abstract: The microtubule-associated protein tau (MAPT) H1 haplotype has been identified as a genetic risk factor for synucleinopathies. However, whether it modulates tau or α-synuclein pathology remains unknown. Our aim was to investigate the relationship between MAPT haplotypes and pathologic aggregates of tau and α-synuclein in pathologically confirmed cases of dementia with Lewy bodies (DLB). Twenty-two cases fulfilling clinical and neuropathological criteria for DLB were included. Clinical and neuropathological data were collected, and APOE and MAPT genotypes were determined. Tau and α-synuclein pathology was assessed semiquantitatively in 17 brain areas and total scores were calculated. DLB H1/H1 (n = 12) and H2 carriers (n = 10) did not differ in demographics, clinical variables, concomitant Alzheimer's pathology, or APOE genotype. Total α-synuclein scores were significantly increased in the H1/H1 group (p = 0.011), largely due to an increase in brainstem regions. This difference was driven by an increase in Lewy bodies and diffuse and punctuate cytoplasmatic α-synuclein aggregates (p = 0.007 and p = 0.025 respectively). These findings provide a mechanistic link for the genetic association between MAPT haplotypes and synucleinopathies.
authors: Neurology Department, Institut d'Investigacions Biomediques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Martí
authors: M
authors: Colom-Cadena
authors: Ellen
authors: E
authors: Gelpi
authors: María J
authors: MJ
authors: Martí
authors: Sara
authors: S
authors: Charif
authors: Oriol
authors: O
authors: Dols-Icardo
authors: Rafael
authors: R
authors: Blesa
authors: Jordi
authors: J
authors: Clarimón
authors: Alberto
authors: A
authors: Lleó
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D020961:Lewy Body Disease / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins