Diagnostic reclassification under the AA-2024 biological framework: A real-world comparison with ATN 2018 using cerebrospinal fluid biomarkers

Background Alzheimer's disease (AD) has evolved from a syndromic diagnosis to a biologically defined entity supported by cerebrospinal fluid (CSF) biomarkers. The Alzheimer's Association 2024 (AA-2024) criteria are expected to expand biological AD classification compared with the 2018 NIA–AA AT(N) framework. Objective To compare biological AD classification using the AT(N) 2018 framework and the AA-2024 criteria in a real-world cohort. Methods We conducted a retrospective study including 146 consecutive patients evaluated for cognitive impairment in a tertiary neurology center who underwent CSF biomarker testing (Aβ 42 , Aβ 40 , Aβ 42 /Aβ 40 ratio, phosphorylated tau, and total tau). Each patient was classified according to AT(N) 2018 and AA-2024 criteria. Diagnostic distributions, reclassification patterns, and agreement (Cohen's κ) were analyzed. Group comparisons used Wilcoxon rank-sum and Fisher's exact tests. Results Under AT(N) 2018, 40/146 (27.4%) patients met biological AD criteria, whereas AA-2024 classified 72/146 (49.3%) as AD. Reclassification occurred exclusively from non-AD to AD (32 patients, 21.9%), with no reverse reclassification. Agreement was moderate (κ = 0.57). Concordant AD cases (AD+/AD+) showed lower Aβ 42 /Aβ 40 ratios and higher total and phosphorylated tau levels than reclassified cases (AD−/AD+) (all p < 0.001), as well as higher neurodegeneration marker positivity (70% versus 25%; p < 0.001). Final clinical AD diagnosis was assigned to 98% of concordant cases versus 38% of reclassified cases (p < 0.001). Conclusions AA-2024 increases biological AD classification by identifying amyloid-positive individuals with lower tau burden and clinical heterogeneity, underscoring the need to integrate biomarker-based definitions with clinical and longitudinal assessment.