Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 312 - 339

Published: Sept. 26, 2019

Language: Английский

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Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors

Science Advances, Journal Year: 2019, Volume and Issue: 5(1)

Published: Jan. 4, 2019

Gingipains from Porphyromonas gingivalis drive Alzheimer’s pathology and can be blocked with small-molecule inhibitors.

Language: Английский

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Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts

The Lancet Neurology, Journal Year: 2020, Volume and Issue: 19(5), P. 422 - 433

Published: April 22, 2020

Language: Английский

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Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

JAMA, Journal Year: 2020, Volume and Issue: 324(8), P. 772 - 772

Published: July 28, 2020

Importance

There are limitations in current diagnostic testing approaches for Alzheimer disease (AD).

Objective

To examine plasma tau phosphorylated at threonine 217 (P-tau217) as a biomarker AD.

Design, Setting, and Participants

Three cross-sectional cohorts: an Arizona-based neuropathology cohort (cohort 1), including 34 participants with AD 47 without (dates of enrollment, May 2007-January 2019); the Swedish BioFINDER-2 2), cognitively unimpaired (n = 301) clinically diagnosed patients mild cognitive impairment (MCI) 178), dementia 121), other neurodegenerative diseases 99) (April 2017-September Colombian autosomal-dominant kindred 3), 365PSEN1E280A mutation carriers 257 noncarriers (December 2013-February 2017).

Exposures

Plasma P-tau217.

Main Outcomes Measures

Primary outcome was discriminative accuracy P-tau217 (clinical or neuropathological diagnosis). Secondary association pathology (determined using positron emission tomography [PET]).

Results

Mean age 83.5 (SD, 8.5) years 1, 69.1 10.3) 2, 35.8 10.7) 3; 38% were women 51% 57% 3. In antemortem differentiated neuropathologically defined from non-AD (area under curve [AUC], 0.89 [95% CI, 0.81-0.97]) significantly higher than P-tau181 neurofilament light chain (NfL) (AUC range, 0.50-0.72;P < .05). The 2 clinical vs (AUC, 0.96 0.93-0.98]) P-tau181, NfL, MRI measures 0.50-0.81;P .001) but not different compared cerebrospinal fluid (CSF) P-tau217, CSF tau-PET 0.90-0.99;P > .15). 3, levels greater amongPSEN1mutation carriers, noncarriers, approximately 25 older, which is 20 prior to estimated onset MCI among carriers. correlated tangles (Spearman ρ 0.64;P .001), 0.15;P .33), β-amyloid plaques 1. discriminated abnormal normal scans 0.93 0.91-0.96]) Aβ42:Aβ40 ratio, 0.67-0.90;P .05), its performance 0.96;P .22).

Conclusions Relevance

Among 1402 3 selected cohorts, diseases, established plasma- MRI-based biomarkers, key CSF- PET-based measures. Further research needed optimize assay, validate findings unselected diverse populations, determine potential role care.

Language: Английский

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Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(3), P. 379 - 386

Published: March 1, 2020

Language: Английский

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A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(2), P. 73 - 88

Published: Jan. 4, 2019

Language: Английский

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Biomarkers for neurodegenerative diseases

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(6), P. 954 - 963

Published: June 1, 2021

Language: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2020, Volume and Issue: 15(1)

Published: July 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Language: Английский

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The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans

Science, Journal Year: 2019, Volume and Issue: 363(6429), P. 880 - 884

Published: Jan. 25, 2019

Sleep may protect the brain from AD Two main proteins accumulate in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau drive damage cognitive decline. deprivation is known increase acutely chronically. Now, Holth et al. show that chronic sleep strongly increases over hours also drives pathology spreading brains of mice humans (see Perspective by Noble Spires-Jones). Thus, have a direct protective effect on key protein pathology. Science , this issue p. 880 ; see 813

Language: Английский

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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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