Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age‐related tauopathy hippocampi DOI Creative Commons
Timothy E. Richardson, Miranda E. Orr,

Timothy C. Orr

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution progression of degeneration amyloid beta (Aβ) deposition.

Language: Английский

Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms DOI Creative Commons
Ahmed Faraz Khan, Yasser Iturria‐Medina

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 23, 2024

Language: Английский

Citations

4
Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging‐based ATN biomarkers DOI Creative Commons
Sayantan Kumar, Tom Earnest, Braden Yang

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

Abstract INTRODUCTION Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer disease (AD) heterogeneity. We employed deep learning‐based multimodal framework analyze individual‐level variation across ATN (amyloid‐tau‐neurodegeneration) imaging biomarkers. METHODS selected cross‐sectional discovery ( n = 665) and replication cohorts 430) with available T1‐weighted magnetic resonance (MRI), amyloid, tau positron emission tomography (PET). Normative estimated abnormal deviations in amyloid‐positive individuals compared amyloid‐negative controls. Regional abnormality patterns were mapped at different clinical group levels assess intra‐group An severity index (DSI) was calculated using both the spatial extent magnitude of ATN. RESULTS Greater heterogeneity observed more severe stages AD. Higher DSI associated worse cognitive function increased risk progression. DISCUSSION Subject‐specific maps reveal heterogeneous impact AD brain. Highlights examined Heterogeneity gray matter atrophy, burden. within‐group for patients advanced dementia stages. Patient‐specific metric summarized neurodegeneration neuropathology. Metric is marker poor brain health can monitor

Language: Английский

Citations

0
Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer’s disease: a comprehensive review of the characteristics and therapeutic strategies DOI Creative Commons
Yunkwon Nam,

Soo Jung Shin,

Vijay Kumar

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 26, 2025

Abstract Alzheimer’s disease (AD) is not a single-cause disease; rather, it complex neurodegenerative involving multiple pathological pathways influenced by various risk factors. Aggregation and accumulation of amyloid beta (Aβ) tau are the most prominent features in brains AD patients. Aggregated Aβ exert neurotoxic effects central nervous system, contributing to pathogenesis progression AD. They also act synergistically cause neurodegeneration, resulting memory loss. In this context, dual inhibition aggregation, or dissociation these two aggregates, considered promising for treatment. Recently, inhibitors capable simultaneously targeting aggregation both have been investigated. Specific amino acid domains associated with their aggregation/dissociation identified. Subsequently, therapeutic agents that prevent promote disaggregation identified/developed. review, we summarize major properties involved as well mechanisms regulate dissociation. This comprehensive review may contribute design discovery next-generation dual-targeting drugs tau, potentially leading development more effective strategies

Language: Английский

Citations

0
Integrative network analysis reveals novel moderators of Aβ-Tau interaction in Alzheimer's disease DOI Creative Commons

Akihiro Kitani,

Yusuke Matsui

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 2, 2025

Language: Английский

Citations

0
Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer’s disease DOI Creative Commons
Ke Ye, Xinyu Han, Maoyi Tian

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 3, 2025

Language: Английский

Citations

0
PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS DOI Creative Commons
Issa Olakunle Yusuf, Sepideh Parsi,

Lyle W. Ostrow

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 192, P. 106414 - 106414

Published: Jan. 21, 2024

Alteration in protein citrullination (PC), a common posttranslational modification (PTM), contributes to pathogenesis various inflammatory disorders. We previously reported that PC and arginine deiminase 2 (PAD2), the predominant enzyme isoform catalyzes this PTM central nervous system (CNS), are altered mouse models of amyotrophic lateral sclerosis (ALS). now demonstrate PAD2 expression human postmortem ALS spinal cord motor cortex compared controls, increasing astrocytes while trending lower neurons. Furthermore, is enriched aggregates contain myelin proteins PLP MBP ALS. These results confirm our findings suggest contribute neurodegeneration

Language: Английский

Citations

2
Biomarker pathway heterogeneity of amyloid‐positive individuals DOI Creative Commons
Lloyd Prosser, Carole H. Sudre, Neil P. Oxtoby

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

In amyloid-positive individuals, disease-related biomarker heterogeneity is understudied.

Language: Английский

Citations

2
Navigating the Alzheimer’s Biomarker Landscape: A Comprehensive Analysis of Fluid-Based Diagnostics DOI Creative Commons

Elsa El Abiad,

Ali Al-Kuwari,

Ubaida Al-Aani

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1901 - 1901

Published: Nov. 18, 2024

Alzheimer's disease (AD) affects a significant portion of the aging population, presenting serious challenge due to limited availability effective therapies during its progression. The advances rapidly, underscoring need for early diagnosis and application preventative measures. Current diagnostic methods AD are often expensive invasive, restricting access general public. One potential solution is use biomarkers, which can facilitate detection treatment through objective, non-invasive, cost-effective evaluations AD. This review critically investigates function role biofluid biomarkers in detecting AD, with specific focus on cerebrospinal fluid (CSF), blood-based, saliva biomarkers.

Language: Английский

Citations

1
Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer's disease pathology among cognitively impaired and unimpaired: A systematic review and meta‐analysis DOI Creative Commons
Mohammad Khalafi, William Jones Dartora, Laura Beth McIntire

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Our review summarizes the diagnostic accuracy of plasma and cerebrospinal fluid (CSF) phosphorylated tau 217 (p‐tau217) in detecting amyloid pathology on positron emission tomography (PET). We systematically reviewed studies that reported CSF p‐tau217, searching MEDLINE/PubMed, Scopus, Web Science through August 2024. The p‐tau217 predicting PET was evaluated 30 studies. Both effectively detect deposition. Plasma showed 82% sensitivity for 83% tau, with 86% specificity, respectively. had 79% 91% 84% specificity. identifies Alzheimer's disease (AD) pathology. comparable to deposition PET. Despite being less sensitive PET, can be an efficient screening tool underlying AD Highlights serves as a viable biomarker alternative due strong concordance between their results. accurately (PET) positivity, exhibiting low rate false negatives positives, thereby establishing it reliable (AD). demonstrates slightly higher positivity compared positivity. predictive among cognitively impaired individuals, unimpaired suggesting its enhanced utility clinical settings.

Language: Английский

Citations

1
Analysing heterogeneity in Alzheimer’s Disease using multimodal normative modelling on ATN biomarkers DOI Creative Commons
Sayantan Kumar, Tom Earnest, Braden Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 17, 2023

Structured Abstract INTRODUCTION Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed deep learning-based multimodal framework analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers. METHODS selected cross-sectional discovery (n = 665) and replication cohorts 430) with available T1-weighted MRI, amyloid tau PET. Normative estimated abnormal deviations in amyloid-positive individuals compared amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels assess intra-group An disease severity index (DSI) was calculated using both the spatial extent magnitude of ATN. RESULTS Greater heterogeneity observed more severe stages AD. Higher DSI associated worse cognitive function increased risk progression. DISCUSSION Subject-specific maps reveal heterogeneous impact AD brain.

Language: Английский

Citations

2