Lesson 1Definitions and current diagnostic criteria (NIA-AA 2011/2018 research framework, IWG)Summarises main diagnostic guidelines for Alzheimer’s disease, including NIA-AA 2011, NIA-AA 2018 research framework, and IWG criteria. Highlights shifts towards biological definitions and what this means for clinic use versus research.
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 certaintyLooks at ways to combine CSF, blood, structural MRI, and PET markers to boost diagnostic confidence. Discusses matching and mismatching patterns, test order, and linking results with clinical signs 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 scans, including when to use them, reasons not to, and reading methods. Discusses regional uptake patterns, measurement tools, pitfalls, and how PET results affect diagnosis and care plans.
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 other conditions. Reviews typical atrophy and low metabolism patterns, measurement tools, and how scans support or question 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 constraintsGives step-by-step ways to choose marker tests considering cost, access, and patient health issues. Stresses matching strategies to the clinical question, healthcare setup, and patient needs while avoiding unnecessary tests.
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 markers Aβ42, Aβ42/40 ratio, total tau, and phosphorylated tau. Explains test methods, cut-off points, typical Alzheimer’s patterns, plus test variations, unclear zones, and other causes of odd 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 markers including plasma p-tau181, p-tau217, Aβ42/40, and neurofilament light. Discusses test reliability, thresholds, sample handling, and how blood tests stack up against CSF and PET in various 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 common and unusual clinical types of Alzheimer’s disease, like memory loss, posterior cortical, language, and frontal types. Reviews progression, daily function decline, and how type links to marker 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 marker-based staging with the AT(N) framework, connecting amyloid, tau, and neurodegeneration markers to clinical stage. Covers staging plans, usual paths, and how AT(N) guides outlook and trial entry.
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 sample handling, test validation, and quality systems for Alzheimer’s markers. Covers lab accreditation, rules, and reporting standards to ensure reliable, useful test results across labs.
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
