MAPT H1 haplotype is associated with enhanced alpha-synuclein deposition in dementia with Lewy bodies

作者：Colom Cadena Marti; Gelpi Ellen; Marti Maria J; Charif Sara; Dols Icardo Oriol; Blesa Rafael; Clarimon Jordi; Lleo Alberto^*

来源：Neurobiology of Aging, 2013, 34(3): 936-942.

DOI：10.1016/j.neurobiolaging.2012.06.015

• Dementia with Lewy bodies
• MAPT haplotype
• Parkinson%26apos
• s disease dementia
• Alzheimer%26apos
• s disease
• Tau
• alpha-synuclein

The microtubule-associated protein tau (MAPT) H1 haplotype has been identified as a genetic risk factor for synucleinopathies. However, whether it modulates tau or alpha-synuclein pathology remains unknown. Our aim was to investigate the relationship between MAPT haplotypes and pathologic aggregates of tau and alpha-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 alpha-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%26apos;s pathology, or APOE genotype. Total alpha-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 alpha-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.

• 出版日期2013-3