Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 30, 2024

Abstract Background Although blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET CSF markers of neurodegenerative disease, little is known about how these predict future brain atrophy cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study Aging (BLSA), we examined whether plasma Alzheimer’s disease (AD) pathology (amyloid-β [Aβ 42/40 ], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal volume loss decline. Additionally, determined sex, APOE ε4 status, amyloid-β status modified associations. Methods Plasma measured using Quanterix SIMOA assays. Regional volumes by 3T MRI, a battery neuropsychological tests assessed five domains. Linear mixed effects models adjusted for demographic factors, kidney function, intracranial (MRI analyses) completed relate baseline performance. Results Brain analyses included 622 participants (mean age ± SD: 70.9 10.2) an average 3.3 MRI scans over 4.7 years. Cognitive performance 674 71.2 10.0) 3.9 assessments 5.7 Higher pTau-181 was steeper declines total gray matter regional several medial temporal regions, whereas higher GFAP greater increases ventricular volume. Baseline Aβ NfL levels not changes Lower (higher burden) faster verbal memory visuospatial performance, fluency. generally consistent across sex status. However, associations increasing significantly stronger among individuals burden, association Conclusions Among older adults, AD (pTau-181) (GFAP), but (NfL), serve

Язык: Английский

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Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics

Biomedicines, Год журнала: 2025, Номер 13(2), С. 279 - 279

Опубликована: Янв. 23, 2025

Alzheimer’s disease (AD) is traditionally viewed through the lens of amyloid cascade hypothesis, implicating amyloid-beta and tau protein aggregates as main pathological culprits. However, burgeoning research points to brain’s resident immune cells, microglia, critical players in AD pathogenesis, progression, potential therapeutic interventions. This review examines dynamic roles microglia within intricate framework AD. We detail involvement these cells neuroinflammation, explaining how their activation response fluctuations may influence trajectory. further elucidate complex relationship between pathology. study highlights dual nature which contribute both aggregation clearance protein. Moreover, an in-depth analysis interplay unveils significant, yet often overlooked, impact this interaction on neurodegeneration Shifting from conventional approaches, we assess current treatments primarily targeting introduce novel strategies that involve manipulating microglial functions. These innovative methods herald a paradigm shift management Finally, explore field precision diagnosis pursuit robust biomarkers. underline more profound comprehension biology could enrich essential areas, potentially paving way for accurate diagnostic tools tailored treatment strategies. In conclusion, expands perspective pathology treatment, drawing attention multifaceted microglia. As continue enhance our understanding microglial-focused interventions emerge promising frontier bolster arsenal fight against

Язык: Английский

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Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION Dual cognitive and mobility decline is more strongly associated with dementia risk than only. It remains unknown whether this syndrome brain atrophy patterns, white matter (WM) damage, or pathology. METHODS In the Baltimore Longitudinal Study of Aging participants without dual decline, we used linear mixed‐effects models to compare up 13‐year longitudinal changes in MRI‐derived WM hyperintensities ( n = 339), microstructure 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ ) ratio 349), phosphorylated tau 181 (pTau181) 258). RESULTS Those experiencing showed accelerated medial temporal p .004), parietotemporal .029), perisylvian regions .028), whereas gait only .035) memory .021). was also unique microstructural deterioration several tracts < .05), a greater decrease Aβ .015), increases GFAP .009) NfL .001). DISCUSSION Individuals are at an increased for regional atrophy, degradation, biomarker‐defined molecular underlying dementia. Highlights patterns. deterioration. ratio. NfL. may indicate blood markers

Язык: Английский

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The moderating effect of diet on the relationship between depressive symptoms and Alzheimer’s disease-related blood-based biomarkers

Neurobiology of Aging, Год журнала: 2025, Номер 147, С. 213 - 222

Опубликована: Янв. 15, 2025

Язык: Английский

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Association of Plasma Biomarkers of Alzheimer Disease and Neurodegeneration With Longitudinal Intra-Network Functional Brain Connectivity

Neurology, Год журнала: 2025, Номер 104(4)

Опубликована: Янв. 31, 2025

Alzheimer disease (AD) is defined by cortical β-amyloid (Aβ), tau, and neurodegeneration, which contribute to cognitive decline, in part, altering large-scale functional brain networks. While Aβ tau have been associated with changes connectivity, it unknown whether plasma biomarkers relate such changes. In a healthy community sample of cognitively unimpaired adults free from major CNS the Baltimore Longitudinal Study Aging, we examined AD pathology (Aβ42/40, phosphorylated [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), neuronal injury (neurofilament light chain [NfL]) were longitudinal connectivity related cognition. Plasma measured using Quanterix SIMOA assays. Intranetwork (3T resting-state fMRI) 7 networks was derived predefined parcellation mask for each participant visit. Cognitive performance assessed concurrently fMRI scan. Covariate-adjusted linear mixed-effect models used determine (1) (2) magnitude biomarker-connectivity relationships differed amyloid status, (3) co-occurred Our primary findings (n = 486; age 65.5 ± 16.2 years; 54% female; mean follow-up time 4.3 1.7 years) showed that higher baseline GFAP faster declines somatomotor (β -0.04, p 0.01, 95% CI -0.06 -0.01), limbic -0.03, 0.02, -0.005), frontoparietal -0.07 -0.01) network connectivity. Amyloid status moderated several associations. For instance, NfL visual but only among amyloid-positive participants. Among 421 participants ≥2 visits (age 71.7 11.4 55% 3.9 1.6 years), concurrent cognition; however, these results did not survive multiple comparison correction. participants, amyloidosis, astrogliosis, are particularly Major limitations include lack inclusion sensitive pTau-217 pTau-231 isoforms comparative PET biomarkers.

Язык: Английский

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The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20‐year dementia risk

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Abstract INTRODUCTION There is an unmet need for tools to quantify dementia risk during its multi‐decade preclinical/prodromal phase, given that current biomarkers predict over shorter follow‐up periods and are specific Alzheimer's disease. METHODS Using high‐throughput proteomic assays machine learning techniques in the Atherosclerosis Risk Communities study ( n = 11,277), we developed Dementia SomaSignal Test (dSST). RESULTS In addition outperforming existing plasma biomarkers, dSST predicted mid‐life a 20‐year across two independent cohorts with different ethnic backgrounds (areas under curve [AUCs]: 0.68–0.70, dSST+age 0.75–0.81). separate cohort, was associated longitudinal declines multiple cognitive domains, accelerated brain atrophy, elevated measures of neuropathology (as evidenced by positron emission tomography biomarkers). DISCUSSION The cost‐effective, scalable, minimally invasive protein‐based prognostic aid can up decades before onset. Highlights (dSST) predicts cohorts. outperforms predicting risk. decline atrophy third cohort. decades.

Язык: Английский

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Elevated Levels of Plasma Phosphorylated Tau 181 (pTau181) Associated With Opioid Use to Guide Medication Titration Over a Clinically Relevant Short Timescale

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

The identification of many medications that delay neurodegeneration in animal models has created too combinations to try patients when time is short. We hypothesized biomarkers premature neuronal aging are part the amyloid-tau-neurodegeneration (ATN) profile, namely amyloid-β ratio, phosphorylated tau 181 (pTau181), and neurofilament light chain (NfL), could provide tools optimize treatment single-patient trials rapidly. retrospectively analyzed these with extensive neuropsychiatric polypharmacy aging. investigated whether ATN profile were associated age, gender, metabolic syndrome markers, medication use. Additionally, two case reports provided examples biomarker application clinical settings. identified 113 plasma profiles. Of 80 those patients, phenotypic data available. Among pTau181 was elevated 31 (38.75%), ratio below normal ranges 11 (13.75%), NfL three (3.75%). correlated as expected. Opioid use significantly (p = 0.004) 0.002), also after Bonferroni correction (both p < 0.05), but not ratio. other It now possible identify overlaps between complex behavioral phenotypes (pain cognition), endophenotypes (ATN profile), medication-targeted components age-related pathophysiology. current study provides a proof concept; future research should focus on aging, where dosage choices based individual To facilitate such trials, funding needed promote repurposed generic treatments, educate providers regarding optimization principles, continue developing sensitive biomarkers. Together, can ensure rapid progress for optimization.

Язык: Английский

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Lifestyle factors and plasma biomarkers of Alzheimer's disease: A narrative review

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100130 - 100130

Опубликована: Март 1, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by amyloid-β (Aβ), tau hyperphosphorylation and neurodegeneration. Blood-based biomarkers are emerging as minimally invasive tool for detection monitoring. This review depicts the relationships between modifiable lifestyle factors (nutrition, physical activity (PA), sleep, alcohol consumption, smoking, social isolation) plasma of AD: Aβ42, Aβ40, Aβ42/40, phosphorylated tau, total neurofilament light chain (NfL) glial fibrillary acidic protein. Limited evidence suggests that better nutrition associated with favourable AD biomarker profiles PA less NfL Aβ, whilst poor sleep elevated Aβ. However, lack data inconsistent findings highlight need further investigation to substantiate or refute these trends. Moreover, future research should include analysis on according gender, metabolic health APOE status. Considering growing emphasis preventing delaying dementia onset justified.

Язык: Английский

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Association of Alzheimer’s disease biomarkers with low premorbid intellectual functioning in a multi-ethnic community-dwelling cohort: A cross-sectional study of HABS-HD

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Background: Individuals with intellectual disability (ID) may have a five-fold increased risk for developing Alzheimer's disease (AD). However, studies investigating brain aging among individuals ID without Down syndrome (DS) are lacking. To begin addressing this gap, our study utilized word reading, widely recognized indicator of an individual's premorbid ability (pIQ), to examine the effects DS on plasma AD biomarker outcomes. Objective: investigate relationship between (pIQ) and biomarkers in DS, while considering ethnic differences these associations. Methods: Participants from Health & Aging Brain Study – Disparities (HABS-HD) were categorized into low (z ≤ −2.00) or average = 0.00 ± 1.00) pIQ groups based reading scores. Plasma including Aβ 40 , 42 42/40 phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), total (t-tau) assayed using Simoa technology. Results: exhibited significantly higher levels p-Tau181 ( p < 0.05), NfL t-tau 0.05) compared those pIQ. Stratified analysis by ethnicity revealed differential associations, Hispanic non-Hispanic White (NHW) participants showing distinct profiles relative Black (NHB) individuals. Conclusions: The findings demonstrate that is reliable factor associated Ethnicity appears modulate suggesting complex interactions factors driving susceptibility across diverse populations. This highlights importance both neurodegenerative processes, particularly non-DS developmental disability.

Язык: Английский

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Plasma GFAP, NfL, and p-tau181 levels as early biomarkers of dementia in Chinese adults: Shenzhen community cohort study

Aging Clinical and Experimental Research, Год журнала: 2025, Номер 37(1)

Опубликована: Март 26, 2025

Язык: Английский

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