Citations 2
Greater burden of Alzheimer's Co-pathology in women with Parkinson's disease dementia
Dunckley, Nathaniel, Driver‐Dunckley, Erika , Zhang, Nan, Serrano, Geidy E., Shill, Holly A., Mehta, Shyamal H. , Belden, Christine, ATRI, A, Beach, Thomas G., Dunckley, Nathaniel, Serrano, Geidy E. , Shill, Holly A. , Belden, Christine M. , Tremblay, Cécilia , Atri, Alireza, Adler, Charles H. , Beach, Thomas G.
Journal of Parkinson’s Disease | July 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Objective To investigate sex differences in Alzheimer's disease (AD) related pathology among autopsy-confirmed Parkinson's disease (PD) cases. Background AD and PD frequently co-occur in older adults, yet the influence of sex on AD pathology in the context of PD remains unexplored. Methods All subjects were enrolled in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP) and had annual standardized research clinical assessments by neuropsychologists, subspecialty behavioral and movement disorders neurologists, as well as comprehensive neuropathological examinations after death. Results Among 230 autopsy-confirmed PD cases, females exhibited greater amyloid plaque pathology burden than males, regardless of a co-occurring AD diagnosis. Specifically, females with PD had significantly higher mean cortical total plaque scores (mean 6.5/15 vs. 4.9/15, p = 0.045) and greater CERAD neuritic plaque density (mean 1.7/3 vs. 1.3/3, p = 0.035). Females were also more likely to have a higher cortical plaque burden (plaque total ≥ 5: 56.8% vs. 39.7%, p = 0.015). In multivariable logistic regression models, female subjects showed greater than twice the odds of having an amyloid plaque burden ≥5 compared to males (OR = 2.18; 95% CI = 1.17–4.06; p = 0.014), when controlling for ApoE ε4 status, Lewy body density score, and age at death. Conclusions Female sex is associated with increased amyloid plaque pathology in PD, independent of ApoE ε4 status. These findings highlight a sex-specific vulnerability to AD pathology in PD patients and support the need for sex-informed approaches to reseach in mixed neurodegenerative disease.
Relationships of CSF biomarkers to cortical atrophy in early‐onset Alzheimer's disease
Touroutoglou, Alexandra, Katsumi, Yuta, Hensel, Jennifer, Schindler, Suzanne E., Ibanez, Laura, Brickhouse, Michael, Eloyan, Ani, Eckbo, Ryan, Zaitsev, Alexander, Joie, Renaud La, Thangarajah, Maryanne, Taurone, Alexander, Vemuri, Prashanthi, Jack, Clifford R., Hammers, Dustin B., Foroud, Tatiana, Aisen, P, Ls, Beckett, Koeppe, Robert, Kukull, Walter A., Toga, Arthur, ATRI, A, Db, Clark, Day, Gregory S., Duara, Ranjan, Graff‐Radford, Neill R., Grant, Ian M., Ls, Honig, Johnson, Erik C. B., Jones, David T., Masdeu, J C, Mf, Mendez, Musiek, Erik, Onyike, Chiadi U., Riddle, Meghan, Rogalski, Emily, Salloway, Stephen, Sha, Sharon, Turner, R. Scott, Wingo, Thomas S., D, Von Dem Wolk, Womack, Kyle, Carrillo, Maria C., Rabinovici, Gil D., Apostolova, L G, JL, Dage, Dickerson, Bradford C., Eldaief, Mark C., Joie, Renaud La , La Joie, Renaud , Touroutoglou, Alexandra , Katsumi, Yuta , Schindler, Suzanne E. , Ibanez, Laura , Brickhouse, Michael , Eloyan, Ani , Thangarajah, Maryanne, Vemuri, Prashanthi , Jack, Clifford R. , Hammers, Dustin B , Foroud, Tatiana , Aisen, Paul , Beckett, Laurel, Koeppe, Robert A. , Kukull, Walter A. , Toga, Arthur W. , Atri, Alireza, Clark, David, Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Johnson, Erik C. B. , Jones, David T. , Musiek, Erik , Onyike, Chiadi U. , Riddle, Meghan , Salloway, Stephen , Sha, Sharon J. , Turner, R. Scott, Wingo, Thomas S , Wolk, David A. , Womack, Kyle , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Dickerson, Bradford Clark , Eldaief, Mark C.
Alzheimer's & Dementia | July 21, 2026 | Volume: 22 | Issue: 7 | Pages: No page available
Abstract INTRODUCTION Although cerebrospinal fluid (CSF) biomarkers reflect neurodegeneration in Alzheimer's disease (AD), it remains unclear whether these biomarkers track neurodegeneration in early‐onset Alzheimer's disease (EOAD). METHODS In 80 EOAD patients, we examined correlations between eight CSF biomarker levels and cortical thickness decreases within the EOAD cortical atrophy signature. Significant correlations were then entered into a multiple regression analysis. We also examined contributions of EOAD atrophy and CSF biomarkers to cognitive impairment. RESULTS The levels of four CSF biomarkers correlated to EOAD signature atrophy. Stepwise regression analyses revealed that CSF neurofilament light chain (NfL) levels best predicted EOAD signature atrophy. Multiple regression showed EOAD signature atrophy combined with CSF NfL levels explained more variance in cognitive impairment than either factor alone. DISCUSSION Within EOAD patients, CSF NfL levels relate to the magnitude of cortical atrophy, and a combination of EOAD signature atrophy and CSF NfL levels most robustly predict cognitive impairment.