Lesson 1Definitions and current diagnostic criteria (NIA-AA 2011/2018 research framework, IWG)Summarizes major diagnostic criteria fi Alzheimer’s disease, includin NIA-AA 2011, NIA-AA 2018 research framework, an IWG criteria. Highlights conceptual shifts toward biological definitions an implications fi clinical versus research use.
Core elements of NIA-AA 2011 clinical criteriaNIA-AA 2018 biological definition and AT(N) useKey features of IWG diagnostic criteriaDifferences between clinical and research criteriaImplications for trial enrollment and labelingLesson 2When and how to combine biomarkers (CSF, blood, PET, MRI) to increase diagnostic certaintyExplores strategies fi combin CSF, blood, structural MRI, an PET biomarkers to boost diagnostic confidence. Discusses concordant an discordant patterns, sequencin tests, an integratin results wid clinical features an disease stage.
Principles of multimodal biomarker integrationCommon concordant and discordant result patternsSequential versus parallel testing strategiesAligning biomarker choice with disease stageCommunicating combined results to patientsLesson 3Molecular neuroimaging: amyloid PET and tau PET — indications, reading, quantitation, and regional patternsFocuses on amyloid an tau PET imaging, includin indications, contraindications, an readin principles. Discusses regional uptake patterns, quantitative metrics, pitfalls, an how PET results influence diagnosis an management decisions.
Appropriate use criteria for amyloid PETTypical amyloid PET regional uptake patternsTau PET tracers and distribution in Alzheimer’sVisual reads versus quantitative PET measuresCommon artifacts and interpretive pitfallsLesson 4Structural and functional imaging: MRI (atrophy patterns, volumetry), FDG-PET — differential diagnostic utilityExplains structural MRI an FDG-PET findings in Alzheimer’s disease an differential diagnoses. Reviews characteristic atrophy an hypometabolism patterns, quantitative tools, an how imaging supports or challenges a suspected diagnosis.
Medial temporal and parietal atrophy patternsVisual rating scales and volumetric quantificationFDG-PET hypometabolism in Alzheimer’s diseaseImaging clues to non-Alzheimer’s dementiasIntegrating MRI and FDG-PET with clinical dataLesson 5Practical algorithms for ordering tests given cost, availability, and patient comorbidity constraintsProvides stepwise approaches to selectin biomarker tests under cost, access, an comorbidity constraints. Emphasizes tailorin strategies to clinical question, healthcare settin, an patient values while avoidin redundant or low-yield testing.
Initial cognitive workup before biomarker testingChoosing CSF versus blood biomarkersWhen to add amyloid or tau PET imagingAdapting algorithms to comorbidities and frailtyCost, insurance coverage, and health system limitsLesson 6Established fluid biomarkers: CSF Aβ42/40, total tau, phosphorylated tau assays — interpretation and limitationsDetails established CSF biomarkers Aβ42, Aβ42/40 ratio, total tau, an phosphorylated tau. Explains assay platforms, cutoffs, an typical Alzheimer’s patterns, as well as analytical variability, gray zones, an non-Alzheimer’s causes of abnormal results.
CSF Aβ42 and Aβ42/40 ratio: biology and cutoffsTotal tau as a marker of neuronal injuryPhosphorylated tau isoforms and assay platformsInterpreting discordant or borderline CSF profilesNon-Alzheimer’s conditions affecting CSF markersLesson 7Blood-based biomarkers: plasma p-tau (181, 217), Aβ42/40, neurofilament light (NfL) — validity, thresholds, and preanalytical issuesCovers blood-based biomarkers includin plasma p-tau181, p-tau217, Aβ42/40, an neurofilament light. Discusses analytical validity, thresholds, preanalytical handlin, an how blood tests compare wid CSF an PET in different settings.
Biology and kinetics of plasma p-tau isoformsPlasma Aβ42/40 ratio and assay approachesNeurofilament light as a nonspecific injury markerPreanalytical factors affecting plasma biomarkersClinical scenarios suited to blood-based testingLesson 8Clinical phenotypes of Alzheimer’s disease and typical progression patternsDescribes typical an atypical clinical phenotypes of Alzheimer’s disease, includin amnestic, posterior cortical, logopenic, an frontal variants. Reviews progression patterns, functional decline, an how phenotype relates to biomarker profiles.
Typical amnestic late-onset Alzheimer’s presentationPosterior cortical atrophy and visuospatial deficitsLogopenic variant primary progressive aphasiaFrontal and behavioral-predominant Alzheimer’sLongitudinal progression and functional milestonesLesson 9Biomarker-based staging (AT(N) framework) and linking biomarkers to clinical stageIntroduces biomarker-based staging usin de AT(N) framework, linkin amyloid, tau, an neurodegeneration markers to clinical stage. Covers staging schemes, typical trajectories, an how AT(N) informs prognosis an trial eligibility.
Conceptual basis of the AT(N) classificationMapping AT(N) profiles to clinical stagesLongitudinal change in AT(N) over the disease courseUsing AT(N) for prognosis and risk communicationLimitations and controversies of AT(N) stagingLesson 10Preanalytical, laboratory quality, and regulatory considerations for biomarker testingReviews preanalytical handlin, assay validation, an quality systems fi Alzheimer’s biomarkers. Covers accreditation, regulatory pathways, an reportin standards to ensure reliable, clinically actionable test results across laboratories.
Sample collection tubes and timing requirementsCentrifugation, aliquoting, and storage conditionsInternal quality control and external proficiency testingRegulatory approval pathways and labeling limitsStandardized reporting formats and reference ranges