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• W3103431558 abstract "Abstract Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, begins to accumulate in the first decades of life in the locus coeruleus (LC), the primary source of cortical norepinephrine. Ensuing dysfunction in noradrenergic neuromodulation is hypothesized to contribute to Alzheimer’s progression. However, research into the role of the LC has been impeded by a lack of effective ways of assessing it in vivo. Advances in high-resolution brainstem magnetic resonance imaging (MRI) hold potential to investigate the association of locus coeruleus integrity and Alzheimer’s-related neuropathological markers in vivo. Leveraging a meta-analytical approach, we first synthesized LC localizations and dimensions across previously published studies to improve the reliability and validity of MR-based locus coeruleus detection. Next, we applied this refined volume of interest to determine whether MR-indexed LC integrity can serve as a marker for noradrenergic degeneration in early-onset Alzheimer’s disease. Eighteen participants (34.7±10.1 years; 9♀) with or known to be at-risk for mutations in genes associated with autosomal-dominant Alzheimer’s disease (ADAD) were investigated. Genotyping confirmed mutations in seven participants (PSEN1, n = 6; APP, n = 1), of which four were symptomatic. Participants underwent 3T-MRI, flortaucipir positron emission tomography (PET), and cognitive testing. LC MRI intensity, a non-invasive proxy for neuronal density, was semi-automatically extracted from high-resolution brainstem scans across the rostrocaudal extent of the nucleus. Relative to healthy controls, symptomatic participants showed lower LC intensity. This effect was pronounced in rostral segments of the nucleus that project to the mediotemporal lobe and other memory-relevant areas. Among carriers of ADAD-causing mutations, closer proximity to the mutation-specific median age of dementia diagnosis was associated with lower LC intensity. Leveraging a multivariate statistical approach, we revealed a pattern of LC-related tau pathology in occipito-temporo-parietal brain regions. Finally, higher locus intensity was closely linked to memory performance across a variety of neuropsychological tests. Our finding of diminished MR-indexed LC integrity in autosomal-dominant Alzheimer’s disease suggest a role of the noradrenergic system in this neurodegenerative disease." @default.
• W3103431558 created "2020-11-23" @default.
• W3103431558 creator A5025126086 @default.
• W3103431558 creator A5028523550 @default.
• W3103431558 creator A5048937263 @default.
• W3103431558 date "2020-10-01" @default.
• W3103431558 modified "2023-09-23" @default.
• W3103431558 title "Lower MR-indexed locus coeruleus integrity in autosomal-dominant Alzheimer’s disease is related to cortical tau burden and memory deficits" @default.
• W3103431558 cites W1489255022 @default.
• W3103431558 cites W1766764214 @default.
• W3103431558 cites W1837231696 @default.
• W3103431558 cites W1947166207 @default.
• W3103431558 cites W1971032265 @default.
• W3103431558 cites W1974146533 @default.
• W3103431558 cites W1975656289 @default.
• W3103431558 cites W1978985638 @default.
• W3103431558 cites W1983182638 @default.
• W3103431558 cites W1991200731 @default.
• W3103431558 cites W1993023011 @default.
• W3103431558 cites W1999785831 @default.
• W3103431558 cites W2006958560 @default.
• W3103431558 cites W2014851815 @default.
• W3103431558 cites W2030325164 @default.
• W3103431558 cites W2031583388 @default.
• W3103431558 cites W2035050487 @default.
• W3103431558 cites W2049247209 @default.
• W3103431558 cites W2058723245 @default.
• W3103431558 cites W2059118547 @default.
• W3103431558 cites W2066912765 @default.
• W3103431558 cites W2073309755 @default.
• W3103431558 cites W2083956595 @default.
• W3103431558 cites W2084943804 @default.
• W3103431558 cites W2086361121 @default.
• W3103431558 cites W2094144144 @default.
• W3103431558 cites W2094384124 @default.
• W3103431558 cites W2095519862 @default.
• W3103431558 cites W2101048381 @default.
• W3103431558 cites W2101135654 @default.
• W3103431558 cites W2102099319 @default.
• W3103431558 cites W2102544039 @default.
• W3103431558 cites W2102595307 @default.
• W3103431558 cites W2104606180 @default.
• W3103431558 cites W2109742329 @default.
• W3103431558 cites W2111968444 @default.
• W3103431558 cites W2116698967 @default.
• W3103431558 cites W2121316843 @default.
• W3103431558 cites W2121671360 @default.
• W3103431558 cites W2126712529 @default.
• W3103431558 cites W2129928127 @default.
• W3103431558 cites W2132842417 @default.
• W3103431558 cites W2136145485 @default.
• W3103431558 cites W2136936410 @default.
• W3103431558 cites W2137226568 @default.
• W3103431558 cites W2144021643 @default.
• W3103431558 cites W2145876795 @default.
• W3103431558 cites W2151721316 @default.
• W3103431558 cites W2159580216 @default.
• W3103431558 cites W2165758561 @default.
• W3103431558 cites W2168451388 @default.
• W3103431558 cites W2170117290 @default.
• W3103431558 cites W2171250577 @default.
• W3103431558 cites W2273698149 @default.
• W3103431558 cites W2276238108 @default.
• W3103431558 cites W2508644210 @default.
• W3103431558 cites W2513816257 @default.
• W3103431558 cites W2563148755 @default.
• W3103431558 cites W2579788133 @default.
• W3103431558 cites W2581791236 @default.
• W3103431558 cites W2716569900 @default.
• W3103431558 cites W2737320535 @default.
• W3103431558 cites W2742369462 @default.
• W3103431558 cites W2752339384 @default.
• W3103431558 cites W2755577678 @default.
• W3103431558 cites W2757253955 @default.
• W3103431558 cites W2760256027 @default.
• W3103431558 cites W2763282512 @default.
• W3103431558 cites W2766247218 @default.
• W3103431558 cites W2767880113 @default.
• W3103431558 cites W2768574326 @default.
• W3103431558 cites W2776257264 @default.
• W3103431558 cites W2777276375 @default.
• W3103431558 cites W2788239274 @default.
• W3103431558 cites W2788770082 @default.
• W3103431558 cites W2800499234 @default.
• W3103431558 cites W2894357926 @default.
• W3103431558 cites W2897780572 @default.
• W3103431558 cites W2900696043 @default.
• W3103431558 cites W2915476106 @default.
• W3103431558 cites W2947548179 @default.
• W3103431558 cites W2948815538 @default.
• W3103431558 cites W2953130519 @default.
• W3103431558 cites W2955273706 @default.
• W3103431558 cites W2964104722 @default.
• W3103431558 cites W2973222021 @default.
• W3103431558 cites W2981007555 @default.
• W3103431558 cites W2996940524 @default.
• W3103431558 cites W2998707549 @default.
• W3103431558 cites W3003504395 @default.
• W3103431558 cites W3014634065 @default.
• W3103431558 cites W3016492427 @default.

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