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Co-existing neuropathological comorbidities have been repeatedly reported to be extremely common in subjects dying with dementia due to Alzheimer disease. As these are likely to be additive to cognitive impairment, and may not be affected by molecularly-specific AD therapeutics, they may cause significant inter-individual response heterogeneity amongst subjects in AD clinical trials. Furthermore, while originally noted for the oldest old, recent reports have now documented high neuropathological comorbidity prevalences in younger old AD subjects, who are more likely to be included in clinical trials.
View Article and Find Full Text PDFCurrent Progress and Future Directions in Non-Alzheimer's Disease Tau PET Tracers.
ACS Chem Neurosci
January 2025
Research Center for Accelerator and Radioisotope Science, Tohoku University, Sendai, Miyagi 980-0845, Japan.
Alzheimer's disease (AD) and non-AD tauopathies are dominant public health issues driven by several factors, especially in the aging population. The discovery of first-generation radiotracers, including [F]FDDNP, [C]PBB3, [F]flortaucipir, and the [F]THK series, for the in vivo detection of tauopathies has marked a significant breakthrough in the fields of neuroscience and radiopharmaceuticals, creating a robust new category of labeled compounds: tau positron emission tomography (PET) tracers. Subsequently, other tau PET tracers with improved binding properties have been developed using various chemical scaffolds to target the three-repeat/four-repeat (3R/4R) tau folds in AD.
View Article and Find Full Text PDFLATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy.
Continuum (Minneap Minn)
December 2024
Article Synopsis
- Alzheimer’s disease (AD) is the most common cause of dementia, but there are other conditions like LATE (limbic-predominant age-related TDP-43 encephalopathy) that also produce similar symptoms, particularly in older adults.
- Recent research shows that LATE can coexist with AD and may occur in individuals with cognitive impairment, leading to difficulty in clinical diagnosis due to the lack of direct biomarkers for TDP-43 pathology.
- Understanding and recognizing non-AD conditions like LATE and primary age-related tauopathy is crucial for neurologists, especially for patients over 75 experiencing slow cognitive decline.
Article Synopsis
- - The emergence of neuropsychiatric symptoms in middle-aged individuals poses diagnostic challenges, making it tough to distinguish between primary psychiatric disorders and early neurodegenerative diseases, especially when brain imaging shows no clear abnormalities.
- - A case study of a 59-year-old woman showed initial symptoms similar to a mood disorder and behavioral frontotemporal dementia, but autopsy revealed a mix of Lewy body disease and tau-related changes.
- - This case highlights the complexities of diagnosing late-onset neuropsychiatric symptoms, underlines their connection to dementia, and stresses the importance of accurate diagnosis for developing targeted therapies and improving clinical trial participation.
Neuropathological Heterogeneity of Dementia Due to Combined Pathology in Aged Patients: Clinicopathological Findings in the Vallecas Alzheimer's Reina Sofía Cohort.
J Clin Med
November 2024
Reina Sofía Alzheimer Center, CIEN Foundation, ISCIII, 28031 Madrid, Spain.
Article Synopsis
- Recent research on late-life dementia highlights both neurodegenerative and vascular conditions contributing to the varied symptoms in patients, utilizing the Vallecas Alzheimer's Reina Sofía (VARS) cohort with over 550 participants and associated brain donations.
- The study focused on 167 patients, primarily older women (79%) with an average age of 88, and found a significant presence of the ApoE-e4 gene variant (43%).
- The main findings revealed that 79.6% had Alzheimer's disease, with a high prevalence of other conditions like vascular dementia and Lewy body dementia, and over 71.1% of the patients showed multiple neuropathological findings, indicating the complexity of dementia in this cohort.
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