Article
Neuroimaging
Valentina Ghisays, Francisco Lopera, Dhruman D. Goradia, Hillary D. Protas, Michael H. Malek-Ahmadi, Yinghua Chen, Vivek Devadas, Ji Luo, Wendy Lee, Ana Baena, Yamile Bocanegra, Edmarie Guzman-Velez, Enmanuelle Pardilla-Delgado, Clara Vila-Castelar, Joshua T. Fox-Fuller, Nan Hu, David Clayton, Ronald G. Thomas, Sergio Alvarez, Alejandro Espinosa, Natalia Acosta-Baena, Margarita M. Giraldo, Silvia Rios-Romenets, Jessica B. Langbaum, Kewei Chen, Yi Su, Pierre N. Tariot, Yakeel T. Quiroz, Eric M. Reiman
Summary: This study utilizes PET measurements to show that cerebellar A beta deposition in CU carriers begins to differ significantly from non-carriers at age 34, 10 years before the estimated onset of mild cognitive impairment. Additionally, cerebellar A beta burden in carriers is associated with age, cortical A beta burden, delayed recall memory, and API ADAD composite score.
NEUROIMAGE-CLINICAL
(2021)
Article
Clinical Neurology
Clara Vila-Castelar, Pierre N. Tariot, Kaycee M. Sink, David Clayton, Jessica B. Langbaum, Ronald G. Thomas, Yinghua Chen, Yi Su, Kewei Chen, Nan Hu, Margarita Giraldo-Chica, Carlos Tobon, Natalia Acosta-Baena, Ernesto Luna, Marisol Londono, Paula Ospina, Victoria Tirado, Claudia Munoz, Eliana Henao, Yamile Bocanegra, Sergio Alvarez, Silvia Rios-Romenets, Valentina Ghisays, Dhruman Goradia, Wendy Lee, Ji Luo, Michael H. Malek-Ahmadi, Hillary D. Protas, Francisco Lopera, Eric M. Reiman, Yakeel T. Quiroz
Summary: This study examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired individuals with and without the Presenilin-1 (PSEN1) E280A mutation. The results suggest that females may have greater cognitive resilience to AD pathology and neurodegeneration than males.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Lara J. Mentink, Joao P. O. F. T. Guimaraes, Myrthe Faber, Emma Sprooten, Marcel G. M. Olde Rikkert, Koen Haak, Christian F. Beckmann
Summary: The study failed to replicate early findings of Filippini et al. but revealed increased functional activation in APOE epsilon 4-carriers during encoding of recollected items, which was also positively associated with polygenic risk score. The results suggest limited genetic effects on brain structure and function in young adults and highlight the complexity of interactions among genetic risk, biomarkers, aging, and lifestyle factors in Alzheimer's disease development.
Review
Cell Biology
Bruno P. Imbimbo, Viviana Triaca, Camillo Imbimbo, Robert Nistico
Summary: This review examines recent clinical trials of investigational drugs for the treatment of neurodegenerative diseases caused by gene mutations or genetic risk factors. The trials focused on subjects with Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and glucocerebrosidase-associated Parkinson's disease. The results of these trials provide valuable insights for future therapeutic approaches.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Smita Patel, Jun Wei, Zhuqing Shi, Andrew S. Rifkin, S. Lilly Zheng, Elizabeth Gelfman, David Duggan, Brian T. Helfand, Peter J. Hulick, Jianfeng Xu
Summary: In a large population-based cohort, not all heterozygous APOE epsilon 4 carriers are at increased risk for Alzheimer's disease (AD). Only epsilon 3/epsilon 4 carriers showed a significantly higher proportion of AD, not epsilon 2/epsilon 4 carriers. Among epsilon 3/epsilon 4 carriers (24% in the cohort), the AD proportion differed significantly based on polygenic risk score (PRS). Particularly, subjects in the bottom 20-percentile PRS had a lower AD proportion compared to the entire cohort, while subjects at the top 5th-percentile PRS had a higher AD proportion than homozygous epsilon 4 carriers. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Eric M. Reiman, Jeremy J. Pruzin, Silvia Rios-Romenets, Chris Brown, Margarita Giraldo, Natalia Acosta-Baena, Carlos Tobon, Nan Hu, Yinghua Chen, Valentina Ghisays, Jessica Enos, Dhruman D. Goradia, Wendy Lee, Ji Luo, Michael Malek-Ahmadi, Hillary Protas, Ronald G. Thomas, Kewei Chen, Yi Su, Connie Boker, Diego Mastroeni, Sergio Alvarez, Yakeel T. Quiroz, Jessica B. Langbaum, Kaycee M. Sink, Francisco Lopera, Pierre N. Tariot
Summary: This article reports the availability and process of accessing baseline data from the API ADAD trial, highlighting the importance of sharing data to accelerate progress in the field and explore important questions related to AD prevention.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Anna Zettergren, Jodie Lord, Nicholas J. Ashton, Andrea L. Benedet, Thomas K. Karikari, Juan Lantero Rodriguez, Anniina Snellman, Marc Suarez-Calvet, Petroula Proitsi, Henrik Zetterberg, Kaj Blennow
Summary: The study revealed that polygenic risk for AD, including APOE, was associated with plasma p-tau181 regardless of diagnostic or A beta pathology status, while polygenic risk for AD beyond APOE was only linked to plasma p-tau181 in individuals with MCI and A beta positivity.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Clinical Neurology
Eva Vasiljevic, Rebecca Langhough Koscik, Erin Jonaitis, Tobey Betthauser, Sterling C. Johnson, Corinne D. Engelman
Summary: This study aimed to characterize the timing of changes in cognitive trajectories related to genetic risk using the APOE score and AD polygenic risk score (PRS). The results showed that cognitive decline differs across time and APOE score, with the trajectories diverging at approximately age 65. The timing of cognitive decline by polygenic risk (including APOE) is similar to APOE alone.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Brian Fulton-Howard, Alison M. Goate, Robert P. Adelson, Jeremy Koppel, Marc L. Gordon, Alzheimer's Disease Genetics Consortium, Nir Barzilai, Gil Atzmon, Peter Davies, Yun Freudenberg-Hua
Summary: The study shows a significant correlation between age-related polygenic risk score and the risk of Alzheimer's disease, particularly in APOE4 carriers. Furthermore, there is a significant difference of 5 years in age at onset between the highest and lowest risk scores among APOE4 carriers.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Linda Gjora, Bjorn Heine Strand, Sverre Bergh, Tom Borza, Anne Braekhus, Knut Engedal, Aud Johannessen, Marte Kvello-Alme, Steinar Krokstad, Gill Livingston, Fiona E. Matthews, Christian Myrstad, Havard Skjellegrind, Pernille Thingstad, Eivind Aakhus, Stina Aam, Geir Selbaek
Summary: A large population-based study in Norway found a higher prevalence of dementia and MCI than previous studies. The standardized prevalence of dementia and MCI in individuals aged 70 and above were 14.6% and 35.3% respectively, with dementia being more prevalent in women and MCI more prevalent in men. The most common subtype of dementia identified was Alzheimer's disease. The study projected a significant increase in the number of individuals with dementia in Norway by 2050 and 2100.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Jarith L. Ebenau, Sven J. Lee, Marc Hulsman, Niccolo Tesi, Iris E. Jansen, Inge M. W. Verberk, Mardou Leeuwenstijn, Charlotte E. Teunissen, Frederik Barkhof, Niels D. Prins, Philip Scheltens, Henne Holstege, Bart N. M. Berckel, Wiesje M. Flier
Summary: The study found that the polygenic risk score and APOE epsilon 4 are associated with amyloid-positive ATN profiles, and can predict the occurrence of AD dementia. When combined in epsilon 4 carriers, a high PRS increases the risk while a low PRS attenuates the risk. Genetic variants beyond APOE play a clinically relevant role in the pathophysiology of AD.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2021)