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

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5143 - 5169

Published: June 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.

Language: Английский

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GFAP as a Potential Biomarker for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1309 - 1309

Published: May 4, 2023

Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer’s disease (AD). Although amyloid-β peptide (Aβ) tau are primarily blood biomarkers, recent studies identified other reliable candidates that can serve as measurable indicators pathological conditions. One such candidate is glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal be detected in samples. Increasing evidence suggests GFAP levels used to detect early-stage AD. In this systematic review meta-analysis, we aimed evaluate peripheral a biomarker AD provide overview regarding its utility. Our analysis revealed level was higher Aβ-positive group than negative groups, individuals with or mild cognitive impairment (MCI) compared healthy controls. Therefore, believe clinical use measurements has potential accelerate diagnosis improve prognosis

Language: Английский

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Predicting amyloid PET and tau PET stages with plasma biomarkers

Brain, Journal Year: 2023, Volume and Issue: 146(5), P. 2029 - 2044

Published: Feb. 15, 2023

Abstract Staging the severity of Alzheimer’s disease pathology using biomarkers is useful for therapeutic trials and clinical prognosis. Disease staging with amyloid tau PET has face validity; however, this would be more practical plasma biomarkers. Our objectives were, first, to examine approaches and, second, prediction stages Participants (n = 1136) were enrolled in either Mayo Clinic Study Aging or Research Center; had a concurrent PET, blood draw; met criteria cognitively unimpaired 864), mild cognitive impairment 148) syndrome dementia 124). The latter two groups combined into impaired group 272). We used multinomial regression models estimate discrimination [concordance (C) statistics] among three (low, intermediate, high), four (Braak 0, 1–2, 3–4, 5–6) stage (none/low versus intermediate/high severity) as predictors separately within individuals. Plasma analytes, p-tau181, Aβ1–42 Aβ1–40 (analysed Aβ42/Aβ40 ratio), glial fibrillary acidic protein neurofilament light chain measured on HD-X Simoa Quanterix platform. p-tau217 was also subset 355) participants Lilly Meso Scale Discovery assay. Models all analytes along risk factors (age, sex APOE) most often provided best (C 0.78–0.82). p-tau181 similar 0.72–0.85 C 0.73–0.86). Discriminating proxy from none/low neuropathological change excellent but not better than only 0.88 0.87 0.91 0.90 impaired). outperformed assay discriminating high intermediate 0.85 0.74) did improve over model 0.83). can discriminate between surrogate accuracy acceptable range. Combinations are single many predictions exception that alone usually performed equivalently combinations discrimination.

Language: Английский

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Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2022, Volume and Issue: 14(1)

Published: Jan. 1, 2022

We explored what combination of blood-based biomarkers (amyloid beta [Aβ]1-42/1-40, phosphorylated tau [p-tau]181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) differentiates Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and with Lewy bodies (DLB). measured the Simoa in two separate cohorts (n = 160 n 152). In one cohort, Aβ1-42/1-40 was also mass spectrometry (MS). assessed differential diagnostic value markers, by logistic regression Wald's backward selection. MS similarly differentiated AD from controls. The panel that optimally FTD consisted NfL p-tau181 (area under curve [AUC] 0.94; cohort 1) or NfL, GFAP, (AUC 0.90; 2). For DLB, p-tau181, GFAP 0.88; 1), only 0.81; A plasma but not Aβ1-42/1-40, might be useful to discriminate AD, FTD, DLB.

Language: Английский

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Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with Aβ‐PET, neurodegeneration, and cognition

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(7), P. 2790 - 2804

Published: Dec. 28, 2022

Abstract Background Glial fibrillary acidic protein (GFAP) is a promising candidate blood‐based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease‐associated changes, clinical correlates, biofluid‐type dependency will influence utility. Methods We evaluated plasma, serum, cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage disease. Results Plasma elevations appear decade before expected onset, after amyloid beta (Aβ) accumulation prior neurodegeneration cognitive decline. distinguished Aβ‐positive from Aβ‐negative ADAD participants showed stronger relationship Aβ load asymptomatic than symptomatic ADAD. Higher plasma was associated degree rate impairment. Serum similar relationships, but these were less pronounced CSF GFAP. Conclusion Our findings support role as Aβ‐related astrocyte reactivity that decline neurodegeneration. Highlights glial (ADAD). positivity increased severity predicted progression. serum carried information ADAD, while did not.

Language: Английский

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Anti‐amyloid antibody treatments for Alzheimer's disease

European Journal of Neurology, Journal Year: 2023, Volume and Issue: 31(2)

Published: Sept. 11, 2023

Abstract Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid‐β. This a joint statement of European Association Neurology and Psychiatric Association. After numerous unsuccessful endeavors create disease‐modifying therapy disease, substantial consistent supporting clinical effectiveness monoclonal antibodies aimed at amyloid‐β finally emerging. The latest trials not only achieved their primary objective slowing progression over several months but also demonstrated positive secondary outcomes decrease in levels as observed through positron emission tomography scans. Taken whole, these findings mark significant breakthrough by substantiating that reducing yields tangible benefits, beyond mere changes biomarkers. Concurrently, regular utilization new generation drugs will determine whether statistical efficacy translates into clinically meaningful improvements. may well signify dawning era development disease.

Language: Английский

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Plasma biomarkers for Alzheimer’s and related dementias: A review and outlook for clinical neuropsychology

Archives of Clinical Neuropsychology, Journal Year: 2024, Volume and Issue: 39(3), P. 313 - 324

Published: March 22, 2024

Recent technological advances have improved the sensitivity and specificity of blood-based biomarkers for Alzheimer's disease related dementias. Accurate quantification amyloid-ß peptide, phosphorylated tau (pTau) isoforms, as well markers neurodegeneration (neurofilament light chain [NfL]) neuro-immune activation (glial fibrillary acidic protein [GFAP] chitinase-3-like 1 [YKL-40]) in blood has allowed researchers to characterize neurobiological processes at scale a cost-effective minimally invasive manner. Although currently used primarily research purposes, these potential be highly impactful clinical setting - aiding diagnosis, predicting risk, monitoring progression. Whereas plasma NfL shown promise non-specific marker neuronal injury, pTau181, pTau217, pTau231, GFAP demonstrated desirable levels identification individuals with pathology dementia. In this forward looking review, we (i) provide an overview most commonly dementias, (ii) discuss how comorbid medical conditions, demographic, genetic factors can inform interpretation biomarkers, (iii) describe ongoing efforts move into clinic, (iv) highlight central role that neuropsychologists may play contextualizing communicating biomarker results patients.

Language: Английский

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Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies

Neurology, Journal Year: 2024, Volume and Issue: 102(12)

Published: June 3, 2024

Plasma β-amyloid-1-42/1-40 (Aβ42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, predictive value dementia with Lewy bodies (DLB). We aimed to evaluate associations these biomarkers CSF amyloid, cognition, core features DLB.

Language: Английский

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Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2485 - 2496

Published: Feb. 8, 2024

Abstract INTRODUCTION Patients with dementia Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate biomarkers of AD and their association positron emission tomography (PET) amyloid tau deposition in the continuum DLB, starting from prodromal stages disease. METHODS The cohort included patients isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment (MCI‐LB), or a concurrent blood draw PET scans. RESULTS Abnormal levels glial fibrillary acidic protein (GFAP) were found at stage MCI‐LB increased PET. phosphorylated (p‐tau)‐181 neurofilament light (NfL) DLB stage. Plasma p‐tau‐181 showed highest accuracy detecting abnormal DLB. DISCUSSION range co‐pathology continuum, particularly GFAP.

Language: Английский

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Clinical and diagnostic implications of Alzheimer’s disease copathology in Lewy body disease

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3325 - 3343

Published: July 11, 2024

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body (LBD), occurring approximately half all cases. Evidence shows that LBD patients with AD copathology show an accelerated course, greater risk cognitive decline and overall poorer prognosis. However, LBD-AD cases may heterogeneous motor non-motor phenotypes higher dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize current understanding by discussing synergistic effects neuropathological changes their clinical relevance. Furthermore, provide extensive overview neuroimaging fluid biomarkers under assessment for use possible diagnostic prognostic values. can predicted vivo means CSF, MRI PET markers, whereas most promising technique to date identifying different biological tissues α-synuclein seed amplification assay. Pathological imaging CSF are associated likelihood but do always mirror severity as pure AD. Implementing blood-based might allow faster screening copathology, thus improving sensitivity LBD-AD. Finally, discuss literature on novel candidate being exploited investigate other aspects neurodegeneration, such neuroaxonal injury, glial activation synaptic dysfunction. The thorough characterization should taken into account when considering differential diagnoses syndromes, evaluation individual level, guide symptomatic disease-modifying therapies.

Language: Английский

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