Lesson 1Definitions and current diagnostic criteria (NIA-AA 2011/2018 research framework, IWG)Summarizes major diagnostic criteria for Alzheimer’s disease, including NIA-AA 2011, NIA-AA 2018 research framework, and IWG criteria. Highlights conceptual shifts toward biological definitions and implications for 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 for combining CSF, blood, structural MRI, and PET biomarkers to improve diagnostic confidence. Discusses concordant and discordant patterns, sequencing tests, and integrating results with clinical features and 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 and tau PET imaging, including indications, contraindications, and reading principles. Discusses regional uptake patterns, quantitative metrics, pitfalls, and how PET results influence diagnosis and 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 and FDG-PET findings in Alzheimer’s disease and differential diagnoses. Reviews characteristic atrophy and hypometabolism patterns, quantitative tools, and 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 selecting biomarker tests under cost, access, and comorbidity constraints. Emphasizes tailoring strategies to clinical question, healthcare setting, and patient values while avoiding 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, and phosphorylated tau. Explains assay platforms, cutoffs, and typical Alzheimer’s patterns, as well as analytical variability, gray zones, and 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 including plasma p-tau181, p-tau217, Aβ42/40, and neurofilament light. Discusses analytical validity, thresholds, preanalytical handling, and how blood tests compare with CSF and 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 and atypical clinical phenotypes of Alzheimer’s disease, including amnestic, posterior cortical, logopenic, and frontal variants. Reviews progression patterns, functional decline, and 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 using the AT(N) framework, linking amyloid, tau, and neurodegeneration markers to clinical stage. Covers staging schemes, typical trajectories, and how AT(N) informs prognosis and 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 handling, assay validation, and quality systems for Alzheimer’s biomarkers. Covers accreditation, regulatory pathways, and reporting 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
