Alzheimer's disease (AD) is the most common cause of dementia, affecting over 55 million people worldwide. For decades, diagnosis was exclusively clinical and occurred when neurodegeneration was already extensive. In 2026, the combination of blood biomarkers, advanced neuroimaging, and the first approved disease-modifying treatments has opened a new era: presymptomatic diagnosis and treatment.
The A/T/N diagnostic framework
The National Institute on Aging and the Alzheimer's Association proposed the A/T/N scheme in 2018 to define Alzheimer's biologically, independent of clinical symptoms. This scheme categorizes biomarkers into three groups:
- A (Amyloid): positive amyloid PET or reduced beta-amyloid 42 in CSF or blood
- T (Tau): positive tau PET or elevated phosphorylated tau (p-tau181, p-tau217, p-tau231) in CSF or blood
- N (Neurodegeneration): MRI atrophy, FDG-PET hypometabolism, or elevated total tau in CSF
An A+/T+/N+ patient has active biological Alzheimer's regardless of whether cognitive symptoms are present — a fundamental conceptual shift since disease-modifying treatments must begin before neurodegeneration is irreversible.
Blood biomarkers: democratizing diagnosis
The validation of plasma biomarkers has been the most transformative advance of the last three years. Plasma p-tau217 has 92% sensitivity and 89% specificity for distinguishing Alzheimer's from other dementias — performance comparable to amyloid PET or CSF analysis, but at radically different cost and accessibility. A blood test can be performed in any clinical laboratory.
The Aβ42/Aβ40 plasma ratio, GFAP (glial fibrillary acidic protein, marker of astrogliosis), and NfL (neurofilament light chain, non-specific axonal damage marker) complete the panel of blood biomarkers validated for clinical use in 2026.
Lecanemab and donanemab: the first disease modifiers
The FDA approval of lecanemab (Leqembi) in July 2023 and its conditional EMA approval in January 2025 represents the first treatment that modifies the biological course of AD. Lecanemab is an anti-amyloid monoclonal antibody that clears amyloid protofibrils from the brain. In the CLARITY AD trial (1,795 patients, 18 months), it reduced cognitive decline by 27% versus placebo, measured by the CDR-SB scale.
Donanemab (Kisunla, FDA-approved July 2024) acts on pyroglutamate amyloid and demonstrated in the TRAILBLAZER-ALZ 2 trial a 35% reduction in cognitive decline in patients with low-intermediate tau burden. A notable advantage is that treatment can be discontinued when amyloid PET normalizes, which occurs in 40% of patients at 6 months and 72% at 12 months.
Both drugs produce amyloid-related imaging abnormalities (ARIA): edema (ARIA-E) or microhemorrhages (ARIA-H). Symptomatic ARIA occurs in 3-6% of patients overall but in 30-40% of homozygous APOE4 carriers, making APOE4 genotyping mandatory before treatment initiation.
Lifestyle intervention: the FINGER study
The FINGER study demonstrated that a multidomain intervention (diet, exercise, cognitive training, and vascular risk factor management) reduces cognitive decline in older adults at elevated risk. A two-year intervention produced a 25% improvement in global cognition versus controls. The WorldWideFINGERS program is now replicating this design across multiple countries.
