Effect of APOE ɛ4 genotype on age at onset and comorbid pathologies in multiple system atrophy (P8-11.004)

Abstract

<h3>Objective:</h3> To elucidate the effect of apolipoprotein (APOE) ɛ4 genotype on age at onset and comorbid pathologies in multiple system atrophy (MSA). <h3>Background:</h3> APOE ɛ4 increases risk of Alzheimer’s disease (AD) and lowers age of onset of late-onset AD. In synucleinopathy, APOE ɛ4 has been reported to correlate with the severity of Lewy body pathology in Lewy body disease and to lower the age of onset of Parkinson’s disease. The association of APOE E4 with MSA is not well understood. <h3>Design/Methods:</h3> This study included 145 pathologically confirmed MSA patients (female 43%) in the Mayo Clinic Brain Bank. We reviewed the medical records to identify the age at onset at which motor or autonomic symptoms presented. MSA patients were divided into two groups: APOE ɛ4 carriers and non-carriers. We examined comorbid pathologies, including AD pathology, Lewy-related pathology, TDP-43 proteinopathy, argyrophilic grains, cerebral amyloid angiopathy (CAA), and aging-related tau astrogliopathy (ARTAG). We defined the presence of AD pathology based on the Braak neurofibrillary tangle stage and the Thal amyloid phase if both were equal or greater than 3. We compared the frequency of each pathology between APOE ɛ4 carriers and non-carriers. <h3>Results:</h3> Among 145 MSA patients, 26% (37/145) had APOE ɛ4 (female 41%) and 74% (108/145) had non-ɛ4 (female 44%). Age at onset was significantly younger in MSA with APOE ɛ4 than non-ɛ4 (P = 0.028, 56 ± 6 vs. 60 ± 10 years old). The frequency of CAA was significantly greater in MSA with APOE ɛ4 than non-ɛ4 (P = 0.0032, 43% vs. 18%); however, there was no significant difference in the frequency of AD pathology, Lewy-related pathology, TDP-43 proteinopathy, argyrophilic grains, and ARTAG. <h3>Conclusions:</h3> Our results indicate that APOE ɛ4 is associated with CAA in MSA, as well as lower age at onset, but not AD or Lewy-related pathologies. <b>Disclosure:</b> Dr. Sekiya has nothing to disclose. Dr. Koga has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Dickson has nothing to disclose.