<p>A biomarker-anchored pathway for diagnosing early-stage Alzheimer’s disease (AD) is emerging, with blood-based biomarker (BBB) testing now available to help triage the use of confirmatory positron emission tomography (PET) scanning or cerebrospinal fluid (CSF) biomarker analysis. Candidacy for disease-modifying therapy (DMT) for both mild cognitive impairment and mild Alzheimer’s dementia is dependent on the presence of amyloid-β (Aβ) pathology, along with APOE- and magnetic resonance imaging (MRI)–informed, amyloid-related imaging abnormalities (ARIA) risk counseling. Maintenance dosing is then individualized between the use of clinic-supervised intravenous (IV) infusion for lecanemab and donanemab and a weekly at-home subcutaneous (SC) injection for lecanemab.</p>

The diagnostic pathway for early AD is shifting from an exclusive reliance on PET scanning and CSF analysis toward practical, validated BBBs, a transition that is aligned with contemporary National Institute on Aging (NIA) and Alzheimer’s Association criteria that include biomarkers in the biological definition of AD. This evolution is accelerated by the May 2025 and October 2025 US Food and Drug Administration (FDA) clearances of the first plasma assays (ie, the Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio [Fujirebio] and the Elecsys pTau181 plasma test [Roche], respectively) to aid in the diagnostic workup of symptomatic adults, underscoring a staged approach in which BBB testing can triage who proceeds to confirmatory PET imaging or CSF biomarker analysis.

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PET and CSF biomarker testing have long anchored the biologic confirmation of AD pathology and remain appropriate confirmatory tests under modern frameworks that position Aβ/tau biomarkers as being central to diagnosis. In parallel, the Alzheimer’s Association released a clinical practice guideline at the Alzheimer’s Association International Conference 2025 that provides brand-agnostic, performance-based recommendations for BBBs in specialty care, including when BBBs can be used up front and when indeterminate or discordant results should trigger PET or CSF biomarker testing. The aforementioned FDA-cleared BBB tests are labeled for symptomatic adults as an aid to identify amyloid pathology, reinforcing that BBBs complement—rather than replace—established confirmatory modalities when diagnostic uncertainty persists.

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Patient selection for anti-amyloid therapy with lecanemab or donanemab for mild cognitive impairment or mild Alzheimer’s dementia is dependent on biomarker-confirmed amyloid positivity, and this is consistent with pivotal clinical trial populations and appropriate-use recommendations. Assessing a patient’s risk for ARIA is a critical step before initiating treatment with DMT; APOE ε4 homozygous carrier status and baseline microhemorrhages are associated with a higher ARIA risk and motivate counseling plus structured surveillance when the decision is made to treat with DMT. APOE-stratified analyses with lecanemab and donanemab highlight a gene dose–dependent ARIA signal supporting informed consent and monitoring plans that reflect individual risk. Real-world evidence is beginning to describe feasibility, safety workflows, and early-use patterns in routine clinical practice, while emphasizing the need for continued longitudinal assessment outside of clinical trials.

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Route- and maintenance-related decisions regarding DMTs increasingly span clinic-supervised IV administration for both lecanemab and donanemab, with an additional SC maintenance option that is now available for lecanemab after the completion of the IV initiation phase. This once-weekly, at-home, SC maintenance dose of lecanemab 360 mg administered via an autoinjector recently received FDA approval for use following an initial 18-month IV course of lecanemab. A recent human factors validation study presented at the Alzheimer’s Association International Conference 2025 showed that most intended users of SC lecanemab successfully administered the full doses under the expected-use conditions, highlighting the feasibility of at-home maintenance dosing. Donanemab remains an IV infusion–only product that is administered every 4 weeks, with a defined uptitration schedule (ie, 350 mg, 700 mg, and 1050 mg for doses 1-3, respectively, then 1400 mg thereafter). Its US prescribing information directs teams to consider stopping treatment with donanemab once amyloid plaques are reduced to minimal levels on an amyloid PET scan, reflecting a treat-to-clearance approach that is unique to its label.

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Supervised IV dosing for either agent centralizes observation for infusion reactions and enables rapid escalation if neurologic symptoms suggest ARIA, an operational advantage that is reflected in appropriate-use recommendations and monitoring reviews for lecanemab and donanemab. FDA-recommended MRI monitoring schedules for the detection of ARIA are specified in labeling and regulatory communications (ie, for lecanemab, MRI prior to infusions 3, 5, 7, and 14 with heightened vigilance during the first 14 weeks; for donanemab, MRI prior to infusions 2, 3, 4, and 7 with heightened vigilance during the first 24 weeks).

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After the IV phase, lecanemab’s weekly SC maintenance dosing may offer advantages that are not observed with the IV course, including less dependence on infusion center appointments, potential reductions in travel and caregiver time, greater flexibility in fitting dosing into household routines, and easier access for patients who live far away from infusion sites. Moreover, this treatment option allows care teams to individualize ongoing therapy around patient preferences, caregiver support, clinical capacity, and imaging logistics, while maintaining the safety surveillance that is stipulated in labeling and appropriate-use guidance.

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A blood-first, confirm-as-needed diagnostic pathway for early AD can streamline the time from clinical suspicion to treatment planning. When combined with structured ARIA risk counseling and shared decision making during the process of choosing between IV and SC maintenance treatment, this pathway can reduce avoidable delays in care without sacrificing safety or equitable access.