Visual Ratings of Medial Temporal Lobe Atrophy correlate with CSF Tau indices in Early-Onset Alzheimer's Disease. (P2.233)

OBJECTIVE: To examine the relationship between regional brain atrophy patterns and cerebrospinal fluid (CSF) biomarker indices across clinical subtypes of early-onset Alzheimer’s disease (EOAD). BACKGROUND: Our prior analyses of biomarkers in EOAD revealed greater elevations of total (tTau) and hyperphosphorylated (pTau) tau in amnestic EOAD and logopenic progressive aphasia (LPA) relative to posterior cortical atrophy (PCA). We sought to determine whether these findings arose from differences in neurofibrillary tangle (NFT) distribution. DESIGN/METHODS: We identified 35 EOAD patients (14 amnestic, 13 LPA, and 8 PCA) with CSF biomarkers and brain magnetic resonance imaging. Two raters used semi-quantitative rating scales to assess atrophy (as a proxy for NFT accumulation) in medial temporal and posterior cortical regions. Ratings were averaged across hemispheres and raters prior to comparison with biomarker indices. RESULTS: CSF tTau (p=0.030) and pTau (p=0.016) levels differed between EOAD subtypes, with the lowest levels seen in PCA. Intraclass correlation coefficients for atrophy ratings (0.79-0.87) suggested excellent agreement between raters. Univariate correlation analyses indicated that higher mean medial temporal lobe atrophy ratings were associated with higher CSF tTau [r(35)=0.35, p=0.039] and pTau [r(32)=0.37, p=0.039] levels. These associations remained significant after adjusting for age, gender, and Mini-Mental Status Examination score (tTau: p=0.003; pTau: p=0.016). Tau indices did not correlate with posterior cortical atrophy ratings. Likewise, Aβ42 levels did not correlate with atrophy in either region. CONCLUSIONS: These results replicate our prior findings of lower tau indices in PCA relative to other EOAD subtypes. Prior studies have reported more medial temporal NFT pathology in amnestic and LPA relative to PCA. Significant correlations between CSF tTau and pTau levels with medial temporal, but not posterior cortical atrophy suggest that the localization of NFTs may modulate CSF tau levels. In particular, medial temporal tau pathology may have greater access to the CSF compartment. Disclosure: Dr. Granadillo has nothing to disclose. Dr. Paholpak has nothing to disclose. Dr. Mendez has received personal compensation in an editorial capacity for UpToDate. Dr. Teng9s spouse holds stock and/or in GE Healthcare and Cerner Corporation.