Citations 2
Greater locus coeruleus vulnerability in atypical clinicopathologic forms of Alzheimer's disease
Dunlop, Sara , Matchett, Billie J. , Mannsbart, Alexander, Al‐Shaikh, Fadi S. Hanna , Rothberg, Darren M., Tranovich, Jessica F., Duara, Ranjan, Uribe, Idaly Vélez, Gondrez, Joselen, Carter, Rickey E., Day, Gregory S., Graff‐Radford, Neill R., Dickson, Dennis W., Grinberg, Lea T., Murray, Melissa E., Day, Gregory S. , Dunlop, Sara Rose, Mannsbart, Alexander F, Peng, Zhongwei , Murray, Melissa E , Day, Gregory S , Duara, Ranjan , Vélez-Uribe, Idaly , Ferman, Tanis J. , Graff‐Radford, Neill R. , Dickson, Dennis W. , Grinberg, Lea T. , Murray, Melissa E.
Alzheimer's & Dementia | February 13, 2026 | Volume: 22 | Issue: 2 | Pages: No page available
Abstract INTRODUCTION The locus coeruleus (LC) degenerates early in Alzheimer's disease (AD). However, the extent of rostrocaudal degeneration across clinicopathologic heterogeneity remains underexplored in AD. METHODS Using digital pathology, we quantified LC neuronal density and area at three neuroanatomic levels in a large AD series. RESULTS Analysis of neuropathologic AD subtypes revealed greater middle LC vulnerability in hippocampal sparing AD compared to typical and limbic predominant AD. Regression analyses identified distinct predictor variables associated with the degeneration of rostral and middle LC. Age at onset predicted 24% of the variability in rostral LC neuronal density, whereas Braak stage, brain weight, Lewy body disease, and age at onset accounted for 15% of the variability in middle LC. Analyses of clinical presentations revealed lower rostral LC neuronal density in non‐amnestic compared to amnestic AD cases. DISCUSSION These insights demonstrate greater LC degeneration in atypical clinicopathologic forms of AD, including hippocampal sparing, young‐onset, and non‐amnestic presentations.
Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci
Ray, Anindita , Chia, Ruth , Rasheed, Memoona, Ece, Bayram, Jinhui, Ding, Walton, Ronald L., Diez-Fairen, Monica, Álvarez, Ignacio Morales, Fanciulli, Alessandra , Seppi, Mag Klaus, Duerr, Susanne, Leys, Fabian , Krismer, Florian , Sidoroff, Victoria , Pirker, Walter , Rascol, Olivier, Foubert-Samier, Alexandra, Meissner, Wassilios G, Tison, François , Barone, Paolo, Russillo, Maria Claudia, Marín-Lahoz, Juan, Kulisevsky, J, Torres, Soraya, Mir, Pablo, Periñán, María Teresa, Proukakis, C., Goh, Yee Yen, Parkkinen, Laura, Hu, Michele T, Saxon, Jennifer A. , Rollinson, Sara , Garland, Emily M. , Litvan, Irene, Alcalay, Roy N, Kwei, Kimberly , Lubbe, Steven, Mao, Qinwen, Flanagan, Margaret E, Castellani, Rudolph J, Ndayisaba, Alain , Calvo, Andrea, Canosa, Antonio, Bohannan, Ryan C., Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Dawson, Ted M, Albert, Marilyn S, Pletniková, Olga , Troncoso, Juan C, Lage, Carmen , Sánchez-Juan, Pascual, Serrano, Geidy E, Beach, Thomas G, Morris, Huw R, Clarimon, Jordi, Jaunmuktane, Zane, Révész, Tamás, Warner, Tom, Hardy, John A, Ryten, Mina, Ferrucci, Luigi, Topol, Eric, Torkamani, Ali, DeCasien, Alex R, Chiò, Adriano, Low, Philip, Wszolek, Zbigniew K, Dickson, Dennis W., Traynor, Bryan J, Gibbs, J Raphael, Dalgard, Clifton L, Ross, Owen A, Houlden, Henry, Scholz, Sonja W., Hardy, John , Dickson, Dennis W. , Ross, Owen A. , Houlden, Henry , Scholz, Sonja W. , Chia, Ruth , Proukakis, Christos , Dickson, Dennis W , Dalgard, Clifton L , Ross, Owen A , Houlden, Henry , Scholz, Sonja W , Hardy, John , Reynolds, Regina H. , Díez-Fairén, Mónica , Fanciulli, Alessandra , Stefanova, Nadia , Seppi, Klaus , Krismer, Florian, Zimprich, Alexander , Rascol, Olivier , Foubert‐Samier, Alexandra , Meissner, Wassilios G. , Tison, François , Traon, Anne Pavy‐Le , Pellecchia, Maria Teresa , Marín‐Lahoz, Juan , Kulisevsky, Jaime , Mir, Pablo , Chelban, Viorica , Wu, Lesley , Kobylecki, Christopher , Biaggioni, Italo , Litvan, Irene , Rubio, Ileana, Lubbe, Steven , Flanagan, Margaret E , Castellani, Rudolph J. , Khurana, Vikram , Mora, Gabriele , Floris, Gianluca , Moore, Anni K. , Norcliffe‐Kaufmann, Lucy , Palma, Jose-Alberto , Kaufmann, Horacio , Dawson, Ted M , Rosenthal, Liana S. , Pantelyat, Alexander , Troncoso, Juan C. , Infante, Jon , Serrano, Geidy E. , Beach, Thomas G. , Pástor, Pau , Albani, Diego , Clarimón, Jordi , Jaunmuktane, Zane , Frontzek, Karl , Warner, Thomas T. , Ferrucci, Luigi , Topol, Eric J. , Torkamani, Ali , DeCasien, Alex R. , Chiò, Adriano , Singer, Wolfgang , Cheshire, William P. , Wszołek, Zbigniew K. , Traynor, Bryan J. , Gibbs, J. Raphael
Brain | February 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The human X chromosome accounts for ∼5% of the genome. Despite its size, the role of X-chromosomal variants in human diseases is not well understood, mainly due to its distinct inheritance pattern and the frequent omission of sex chromosomes from genome-wide association studies. This study used whole-genome sequencing data from 888 multiple system atrophy (MSA) cases and 7128 controls to perform an X-chromosome-wide common variant association study. Our analyses revealed two sex-differential risk loci: one located at Xq28, associated with increased risk for MSA in females [index variant: rs4898389, odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.40–2.03, P-value = 2.43 × 10⁻⁸], and another at Xp22.2 within the TBL1X gene, identified in males (index variant: rs6638956, OR = 1.48, 95%CI = 1.26–1.73, P-value = 9.92 × 10⁻⁷). In the Xq28 locus, colocalization analyses pointed to FAM3A and PLXNA3 as genes of interest. These findings emphasize the vital role of sex-differential genetic factors in the pathogenesis of MSA.