Striatal tau burden is increased in APOE-ϵ4+ mild cognitive impairment

BackgroundThe presence of {beta}-amyloid (A{beta}) extracellular plaques and hyper-phosphorylated tau neurofibrillary tangles characterize the pathology of Alzheimers disease (AD) and mild cognitive impairment (MCI). Individuals carrying the apolipoprotein E-{varepsilon}4 (APOE-{varepsilon}4) allele are at increased risk of cognitive decline and developing AD pathology. The 18F-AV1451 radioligand allows for assessment of tau burden in vivo. However, this radioligand also binds with iron and this off-target binding can occlude tau deposition in iron rich gray matter structures such as the putamen and caudate nucleus. MethodsWe employ a MRI measure sensitive to iron, quantitative susceptibility mapping, to control for off-target binding effects of the 18F-AV1451 radioligand and examine tau burden in the striatum. 20 APOE-{varepsilon}4 negative MCI, 20 APOE-{varepsilon}4 positive MCI, and 29 APOE-{varepsilon}4 negative control participants from ADNI were used in this analysis. ResultsIncreased tau pathology (18F-AV1451 PET uptake), after controlling for tissue susceptibility, was found in the putamen and caudate nucleus of APOE-{varepsilon}4+ MCI participants as compared to APOE-{varepsilon}4 negative MCI and control participants. Tau burden in the caudate nucleus of the APOE-{varepsilon}4+ MCI group was correlated with Montreal Cognitive Assessment (MOCA) score with higher caudate tau burden associated with greater cognitive impairment. ConclusionsControlling for iron allows for the assessment of tau burden in iron rich deep gray matter structures. Our findings suggest that APOE-{varepsilon}4 allele increases the risk of developing AD pathology in the striatum.