Diagnosis

Clinical assessment

The diagnostic process still begins with a clinical evaluation by a primary care physician or specialist. Brief cognitive screens — MoCA, MMSE — and a structured history with the patient and a knowledgeable informant are the entry points. Biomarker testing has not displaced this step.

Plasma biomarkers

Plasma assays — primarily plasma p-tau217 — have crossed into routine clinical use as triage and rule-in / rule-out tools in symptomatic populations. Several FDA-cleared in-vitro diagnostics are now available alongside laboratory-developed tests. Pre-analytical handling matters more than for routine clinical chemistry, and performance varies across populations not represented in the original validation cohorts.

See our Insight on how blood biomarkers reshape diagnosis for a fuller treatment.

Cerebrospinal fluid panels

CSF testing — Aβ42/40 ratio, p-tau, total tau — remains highly validated and widely used for diagnostic confirmation, particularly when plasma results are equivocal or the clinical picture is atypical. Lumbar puncture is well-tolerated by most patients but the procedural friction is real, especially in community-practice settings.

Amyloid and tau PET imaging

Amyloid PET is clinically validated, Medicare-covered for diagnostic clarification under defined indications, and is the standard confirmatory test before initiating disease-modifying therapy at most centers. Tau PET is available at fewer sites and used more selectively — for prognostication and for trial-related work.

Genetic testing

APOE genotyping is now de facto standard before initiating anti-amyloid therapy, given the meaningfully higher ARIA risk in homozygotes. Counselling capacity is a known constraint. See our Explainer on why APOE4 matters.

The shift toward earlier detection

The combination of validated plasma assays, accessible amyloid PET, and growing public awareness has pulled diagnosis earlier in the disease course. The treatment-eligible population — early symptomatic, amyloid- confirmed — is now identifiable in a way that was not operationally possible five years ago. The question that follows is whether the downstream system has the capacity to support what early diagnosis implies for treatment, monitoring, and counselling.