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Silencing Apoe with divalent-siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease
DISCUSSION: These results establish siRNA-based modulation of Apoe as a viable therapeutic approach, highlight immune activation as a key pathway affected by Apoe modulation, and provide the technology to further evaluate the impact of APOE silencing on neurodegeneration.PMID:38375983 | DOI:10.1002/alz.13703 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - February 20, 2024 Category: Psychiatry Authors: Chantal M Ferguson Samuel Hildebrand Bruno M D C Godinho Julianna Buchwald Dimas Echeverria Andrew Coles Anastasia Grigorenko Lorenc Vangjeli Jacquelyn Sousa Nicholas McHugh Matthew Hassler Francesco Santarelli Michael T Heneka Evgeny Rogaev Anastasia Khv Source Type: research

Protective effect of bilingualism on aging, MCI, and dementia: A community-based study
DISCUSSION: The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life.HIGHLIGHTS: Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code-switching contexts. Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals. Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants ...
Source: The Journal of Alzheimers Association - February 20, 2024 Category: Psychiatry Authors: Aparna Venugopal Avanthi Paplikar Feba Anna Varghese Nithin Thanissery Divya Ballal Rakshith Maneshwar Hoskeri Revathi Shekar Binukumar Bhaskarapillai Faheem Arshad Vandana Valiyaparambath Purushothaman Aravind Banavaram Anniappan Girish Nagaraja Rao Suva Source Type: research

Three-dimensional histology reveals dissociable human hippocampal long-axis gradients of Alzheimer's pathology
CONCLUSION: Path2MR, which enables 3D histology using any brain bank data set, revealed significant differences along the hippocampus between tau and Aβ.HIGHLIGHTS: Path2MR enables three-dimensional (3D) brain reconstruction from blockface dissection photographs. This pipeline does not require dense specimen sampling or a subject-specific magnetic resonance (MR) image. Anatomically consistent mapping of hippocampal sections was obtained with Path2MR. Our analyses revealed an anterior-posterior gradient of hippocampal tau pathology. In contrast, the peak of amyloid-beta (Aβ) deposition was closer to the hippocampal body.P...
Source: The Journal of Alzheimers Association - February 19, 2024 Category: Psychiatry Authors: Diana Ortega-Cruz Kimberly S Bress Harshvardhan Gazula Alberto Rabano Juan Eugenio Iglesias Bryan A Strange Source Type: research

Tracing synaptic loss in Alzheimer's brain with SV2A PET-tracer UCB-J
DISCUSSION: We demonstrate that UCB-J could target SV2A protein with high specificity and depict synaptic loss at synaptosome levels in AD brain regions compared to CNs. UCB-J showed highest synaptic loss in AD hippocampus followed in descending order by frontal cortex, temporal cortex, parietal cortex, and cerebellum. 3 H-UCB-J large brain-section autoradiography and cellular/subcellular fractions binding studies indicated potential off-target interaction with phosphorylated tau (p-tau) species in AD brains, which could have subsequent clinical implications for imaging studies.HIGHLIGHTS: Synaptic positron emission tomogr...
Source: The Journal of Alzheimers Association - February 16, 2024 Category: Psychiatry Authors: Amit Kumar Miriam Scarpa Agneta Nordberg Source Type: research

The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care
DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial.PMID:38358084 | DOI:10.1002/alz.13698 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - February 15, 2024 Category: Psychiatry Authors: Mia Yang Rafael Samper-Ternent Elena Volpi Aval-Na'Ree Green Maya Lichtenstein Katy Araujo Pamela Borek Peter Charpentier James Dziura Thomas M Gill Rebecca Galloway Erich J Greene Kristin Lenoir Peter Peduzzi Can Meng Jordan Reese Amy Shelton Eleni A Sko Source Type: research

Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology
DISCUSSION: AD and LBPs modify risk factors for CAA and should be considered in reviewing the risk of CAA.HIGHLIGHTS: Lewy body pathology modifies risk factors for cerebral amyloid angiopathy (CAA) when present along with Alzheimer's disease (AD) neuropathology. In the context of anti-amyloid monoclonal therapies and their associated risks for hemorrhage, the risk of underlying CAA in mixed dementia with Lewy body pathology needs to be considered.PMID:38353367 | DOI:10.1002/alz.13704 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - February 14, 2024 Category: Psychiatry Authors: Jagan A Pillai James Bena Babak Tousi Kasia Rothenberg C Dirk Keene James B Leverenz Source Type: research

Speech patterns during memory recall relates to early tau burden across adulthood
We examined 238 cognitively unimpaired adults from the Framingham Heart Study (32-75 years) who completed amyloid and tau PET imaging. Speech patterns during delayed recall of a story memory task were quantified via five speech markers, and their associations with global amyloid status and regional tau signal were examined.RESULTS: Total utterance time, number of between-utterance pauses, speech rate, and percentage of unique words significantly correlated with delayed recall score although the shared variance was low (2%-15%). Delayed recall score was not significantly different between β-amyoid-positive (Aβ+) and -nega...
Source: The Journal of Alzheimers Association - February 13, 2024 Category: Psychiatry Authors: Christina B Young Viktorija Smith Cody Karjadi Selah-Marie Grogan Ting Fang Alvin Ang Philip S Insel Victor W Henderson Meghan Sumner Kathleen L Poston Rhoda Au Elizabeth C Mormino Source Type: research

INviting Veterans InTo Enrollment in Alzheimer's Disease Research Centers (INVITE-ADRC): An NIA and VA-sponsored initiative to increase veteran participation in aging and dementia research
CONCLUSIONS: This initiative laid the groundwork to establish sustainable relationships between the VA and ADRCs. The partnership between both federal agencies demonstrates how mutual interests can accelerate progress. In turn, efforts can help our aging veterans.PMID:38348782 | DOI:10.1002/alz.13725 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - February 13, 2024 Category: Psychiatry Authors: Claudia B Padula Sherry Ball Mary F Wyman Kirsten Evans Harli Grant Vyjeyanthi S Periyakoil Carolyn W Zhu Kristine Yaffe Grant D Huang Source Type: research

Gene replacement-Alzheimer's disease (GR-AD): Modeling the genetics of human dementias in mice
Alzheimers Dement. 2024 Feb 11. doi: 10.1002/alz.13730. Online ahead of print.ABSTRACTINTRODUCTION: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible.MET...
Source: The Journal of Alzheimers Association - February 12, 2024 Category: Psychiatry Authors: Kellie Benzow Kul Karanjeet Adrian L Oblak Gregory W Carter Michael Sasner Michael D Koob Source Type: research

Differential DNA methylation in the brain as potential mediator of the association between traffic-related PM < sub > 2.5 < /sub > and neuropathology markers of Alzheimer's disease
DISCUSSION: Our findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM2.5 and AD.HIGHLIGHTS: First study to evaluate the potential mediation effect of DNA methylation for the association between PM2.5 exposure and neuropathological changes of Alzheimer's disease. Study was based on brain tissues rarely investigated in previous air pollution research. Cg10495669, assigned to RBCK1 gene playing a role in inflammation, was associated consistently with 1-year, 3-year, and 5-year traffic-related PM2.5 exposures prior to death. Meet-in-the-middle approach and high-dime...
Source: The Journal of Alzheimers Association - February 12, 2024 Category: Psychiatry Authors: Zhenjiang Li Donghai Liang Stefanie Ebelt Marla Gearing Michael S Kobor Chaini Konwar Julie L Maclsaac Kristy Dever Aliza P Wingo Allan I Levey James J Lah Thomas S Wingo Anke H üls Source Type: research

Brain artery diameters and risk of dementia and stroke
DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.PMID:38332543 | DOI:10.1002/alz.13712 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - February 9, 2024 Category: Psychiatry Authors: Jesus D Melgarejo Kursat Gurel Cassidy Rose Compton Minghua Liu Vanessa Guzman Stephanie Assuras Bonnie E Levin Mitchell S V Elkind M Kamran Ikram Maryam Kavousi M Arfan Ikram Clinton Wright Fabrice Crivello Alexandre Laurent Christophe Tzourio Meike W Ve Source Type: research

Tau accumulation and atrophy predict amyloid independent cognitive decline in aging
DISCUSSION: Our results show that longitudinal Aβ is linked to cognitive decline only in the presence of elevated Aβ, but longitudinal temporal lobe tau is associated with memory decline regardless of Aβ status.HIGHLIGHTS: Entorhinal tau change was associated with memory decline in older adults (OA), regardless of amyloid beta (Aβ). Greater meta-region of interest (ROI) tau change correlated with memory decline in Aβ+ OA. Voxel-wise temporal tau change correlated with memory decline, regardless of Aβ. Meta-ROI tau and global amyloid change correlated with non-memory change in Aβ+ OA. Tau and amyloid accumulation wer...
Source: The Journal of Alzheimers Association - February 9, 2024 Category: Psychiatry Authors: Corrina S Fonseca Suzanne L Baker Lindsey Dobyns Mustafa Janabi William J Jagust Theresa M Harrison Source Type: research