Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(8), С. 5143 - 5169

Опубликована: Июнь 27, 2024

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 single 2012 2018 to create recommendations for diagnosis characterization of disease (AD). present document updates research framework response several recent developments. Defining diseases biologically, rather than based syndromic presentation, has long been standard many areas medicine (e.g., oncology), is becoming a unifying concept common all neurodegenerative diseases, not just AD. consistent with this principle. Our intent objective criteria staging AD, incorporating advances biomarkers, serve as bridge between clinical care. These are intended provide step‐by‐step practice guidelines workflow or specific treatment protocols, but general principles inform AD that reflect current science. Highlights We define (AD) be biological process begins appearance neuropathologic change (ADNPC) while people asymptomatic. Progression burden leads later progression symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid accurate plasma [especially phosphorylated tau 217]) map onto either amyloid beta tauopathy pathway; however, these presence ADNPC more generally (i.e., both neuritic plaques tangles). An abnormal biomarker result sufficient establish decision making throughout continuum. Later‐changing 2 (biofluid PET) can prognostic information, when abnormal, will increase confidence contributing integrated scheme described accommodates fact copathologies, cognitive reserve, resistance may modify relationships stages.

Язык: Английский

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Introducing neurofilament light chain measure in psychiatry: current evidence, opportunities, and pitfalls

Molecular Psychiatry, Год журнала: 2024, Номер 29(8), С. 2543 - 2559

Опубликована: Март 19, 2024

Abstract The recent introduction of new-generation immunoassay methods allows the reliable quantification structural brain markers in peripheral matrices. Neurofilament light chain (NfL), a neuron-specific cytoskeletal component released extracellular matrices after neuroaxonal impairment, is considered promising blood marker active pathology. Given its sensitivity to wide range neuropathological alterations, NfL has been suggested for use clinical practice as highly sensitive, but unspecific tool quantify While large efforts have put characterizing profile many neurological conditions, received far less attention potential biomarker major psychiatric disorders. Therefore, we briefly introduce injury, systematically review findings on cerebrospinal fluid and levels patients with primary conditions highlight opportunities pitfalls. Current evidence suggests an elevation depression, bipolar disorder, psychotic disorders, anorexia nervosa, substance disorders compared physiological states. However, strongly vary across diagnostic entities, stage, patient subgroups, are influenced by several demographic, clinical, analytical factors, which require accurate characterization. Potential applications measure psychiatry seen prognostic algorithms, exclude neurodegenerative disease, assessment toxicity different pharmacological compounds, longitudinal monitoring treatment response. high inter-individual variability lack neurobiological understanding release some main current limitations. Overall, this primer aims researchers clinicians field provide conceptual framework future research directions.

Язык: Английский

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Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Май 15, 2024

Abstract Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades research clinical investigation. This might be partly due a lack widely available cost-effective modalities for diagnosis prognosis. Recently, blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity precision assays measurement platforms. Several biomarkers have shown high potential accurately detecting pathophysiology. As result, there been considerable interest in applying these prognosis, as surrogate metrics investigate impact various covariates on pathophysiology accelerate therapeutic trials monitor treatment effects. However, standardization how blood samples collected, processed, stored analyzed reported can affect reproducibility measurements, potentially hindering toward their widespread use settings. To help address issues, we provide fundamental guidelines developed according recent findings sample handling measurements. These cover important considerations including study design, collection, processing, biobanking, measurement, result reporting. Furthermore, proposed include best practices appropriate procedures genetic ribonucleic acid analyses. While focus key AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau glial fibrillary acidic protein), anticipate that will generally applicable other types biomarkers. We also assist investigators planning executing research, enabling harmonization improve comparability across studies.

Язык: Английский

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Blood phosphorylated Tau181 reliably differentiates amyloid‐positive from amyloid‐negative subjects in the Alzheimer's disease continuum: A systematic review and meta‐analysis

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 1, 2025

Abstract INTRODUCTION Blood‐based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD). METHODS We performed a systematic review and meta‐analysis on potential blood phosphorylated Tau181 (p‐tau181) to differentiate amyloid‐positive (A+) amyloid‐negative (A−) subjects. Two meta‐analyses were conducted, showing mean p‐tau values in cerebrospinal fluid (CSF) A+ A− group, second comparing concentrations CSF among versus A‐ participants, by laboratory assessment method. RESULTS Eighteen studies (2764 5646 subjects) included. The single‐group showed higher p‐tau181 than group. In head‐to‐head meta‐analysis, reliably differentiated patients from participants. DISCUSSION Regardless technique, differentiates Therefore, it might have important applications early inclusion clinical trials AD patients. Highlights role blood‐based discriminating is still uncertain. Blood distinguishes allow trials.

Язык: Английский

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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals

Alzheimer s & Dementia, Год журнала: 2023, Номер 20(2), С. 1284 - 1297

Опубликована: Ноя. 20, 2023

Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.

Язык: Английский

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A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 14, 2024

Abstract Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET memory clinic patients subjective cognitive decline, mild impairment or dementia, the Swedish BioFINDER-2 study (n = 548) TRIAD 179). For each plasma biomarker, cutoffs determined 90%, 95%, 97.5% sensitivity detect tau-PET-positivity. We calculated percentage of below (who would not undergo tau-PET; “saved scans”) tau-PET-positivity rate among participants above “positive predictive value”). Generally, pTau217 performed best. At 95% cutoff both cohorts, resulted avoiding nearly half scans, a those who be referred around 70%. And although was strongly associated subsequent it predicted decline only individuals referral on supporting that this workflow could reduce prognostically uninformative scans. In conclusion, selection tau-PET, when accurate information is clinical value.

Язык: Английский

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Influence of Physiological Variables and Comorbidities on Plasma Aβ40, Aβ42, and p-tau181 Levels in Cognitively Unimpaired Individuals

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1481 - 1481

Опубликована: Янв. 25, 2024

Plasma biomarkers for Alzheimer’s disease (AD) are a promising tool that may help in early diagnosis. However, their levels be influenced by physiological parameters and comorbidities should considered before they can used at the population level. For this purpose, we assessed influences of different on AD plasma markers 208 cognitively unimpaired subjects. We analyzed both cerebrospinal fluid Aβ40, Aβ42, p-tau181 using fully automated Lumipulse platform. The relationships between variables were studied linear regression models. mean differences according to comorbidity groups also studied. glomerular filtration rate showed an influence Aβ40 Aβ42 but not Aβ42/Aβ40 ratio. amyloid ratio was significantly lower diabetic hypertensive subjects, higher have inverse relationship ratio, suggesting latter is more stable marker use general population. Cardiovascular risk factors might long-term effect p-tau181.

Язык: Английский

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Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер 12(1), С. 100022 - 100022

Опубликована: Янв. 1, 2025

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval three amyloid-targeting therapies in US and several other countries, represents a significant development treatment landscape, offering new hope addressing this once untreatable chronic progressive disease. However, challenges persist that could impede successful integration class drugs into clinical practice. These include determining patient eligibility, appropriate use diagnostic tools genetic testing care pathways, effective detection monitoring side effects, improving healthcare system's readiness by engaging both primary dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well cost-effectiveness reimbursement issues. This article brings together insights from diverse group international researchers experts outlines potential opportunities, urging all stakeholders prepare introduction DMTs. We emphasize need develop criteria, including characteristics, specifically European system, ensure administered most suitable patients. It is crucial improve skills knowledge physicians accurately interpret biomarker results, share decision-making patients, recognize treatment-related monitor long-term treatment. advocate investment registries unbiased follow-up studies better understand effectiveness, evaluate optimize Utilizing starting point combination should also be priority.

Язык: Английский

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Detection of Alzheimer Neuropathology in Alzheimer and Non-Alzheimer Clinical Syndromes With Blood-Based Biomarkers

JAMA Neurology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Importance Blood-based biomarkers for Alzheimer disease (AD) are clinically available, but their value is not well understood in syndromes typically associated with frontotemporal lobar degeneration (FTLD). Objective To investigate the clinical importance and detectability of AD FTLD-related neurodegenerative using 3 plasma biomarkers, phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP). Design, Setting, Participants This clinicopathological study took place at University California San Francisco Disease Research Center from August 2008 to July 2022. Autopsied individuals evaluation neuropathological examination, diagnosed related (n = 125), (FTLD; n 198), or cognitively unimpaired (CU) time 16) were included. Exposures AD-related CU. Main Outcomes Measures P-tau217, NfL, GFAP measured single-molecule array (SIMOA). was defined as intermediate high change (ADNC) autopsy. Clinical biomarker associations evaluated linear regressions. Imaging analyses used bayesian mixed-effects modeling. Results A total 349 (191 [55%] male; mean [SD] age death, 72 [11] years) common both (110/125 [88%]) (45/198 [23%]). Neuropathological stage autopsy higher (high ADNC: 82/88 [93%] vs 13/23 [56%] FTLD), frequently considered a copathology (30/198 [15%]). Plasma p-tau217 concentrations (mean [SD], 0.28 [0.16] pg/mL) than 0.10 [0.09] ( P < .05). highest atypical 0.33 [0.02] pg/mL), followed by typical late-onset amnestic 0.27 [0.03] pg/mL). 0.19 compared without 0.07 [0.00] detected neuropathology across (area under receiver operating characteristic curve [AUC], 0.95; 95% CI, 0.93-0.97), slightly better performance (AUC, 0.98; 0.95-1.00) 0.89; 0.83-0.94). NfL had lower detecting 0.73; 0.68-0.78 AUC, 0.75; 0.67-0.80, respectively) added little no diagnostic either alone combinations p-tau217. The presence Mini-Mental State Examination score −2.90 [1.09]; .05), worse on memory z score, −0.64 [0.32]), executive −0.74 [0.19]), visuospatial composites −0.88 [0.37]) increased rates posterior cortical atrophy. Conclusion Clinically relevant prevalent detectable may be useful tool impact non-AD syndromes, including effect disease-modifying therapies.

Язык: Английский

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Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease

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

Опубликована: Июль 6, 2024

Abstract Background With the approval of disease-modifying treatments (DMTs) for early Alzheimer’s disease (AD), there is an increased need efficient and non-invasive detection methods cerebral amyloid-β (Aβ) pathology. Current methods, including positron emission tomography (PET) cerebrospinal fluid (CSF) analysis, are costly invasive that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates efficacy one- two-cutoff strategies determining DMT Butler Hospital Memory & Aging Program (MAP). Methods In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 using site-specific BioFINDER-2 training data, which were then tested in potential candidates from MAP (total n = 150). ROC analysis was used calculate area under curve (AUC) accuracy interpretation strategies, Aβ-PET/CSF testing as standard truth. Results Potential (n 50), primarily diagnosed mild cognitive impairment 29 [58%]) or dementia (21 [42%]), predominantly Aβ-positive (38 [76%]), half (25 [50%]) subsequently treated aducanumab. Elevated predicted Aβ positivity (AUC 0.97 [0.92–1]), ranging 0.88 (0.76–0.95, p 0.028) 0.96 (0.86–1, < .001). When cutoffs, subset (10%) exhibited borderline (between 0.273 0.399 pg/mL) would have potentially required confirmatory testing. Conclusions included participants aducanumab, confirms utility interpreting plasma assessing eligibility. Using could replace more all aducanumab-treated been deemed eligible based on P-tau217. However, false positives remain concern, particularly when applying externally derived lower specificity led inappropriate Aβ-negative participants. Future research should focus prospective validation enhance their generalizability inform standardized decision-making across diverse populations.

Язык: Английский

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