Objective: To identify patients with atypical presentations of Alzheimer’s disease (AD) associated with movement disorders and to characterize their clinical features and CSF biomarker profiles according to the AT(N) framework.

Background: Cerebrospinal fluid (CSF) biomarkers support the biological diagnosis of neurodegenerative diseases and the biomarker-based definition of AD (1,2). Atypical AD presentations may include movement disorders (1,3). In these cases, CSF biomarkers help differentiate AD pathology from other neurodegenerative conditions (2,4).

Method: This retrospective cross-sectional study was conducted within an ongoing AD biomarker cohort at a cognitive and behavioral neurology clinic at Hospital Geral de Fortaleza, Ceará, Brazil. A convenience sample of 147 patients referred for cognitive complaints underwent CSF biomarker analysis, including Aβ42, Aβ40, phosphorylated tau (p-tau), total tau, and Aβ42/40 ratio. Alpha-synuclein was not measured due to assay unavailability at the center. Participants were classified according to the AA 2024 AT(N) criteria for AD. Statistical analysis was performed using SPSS v26 (p<0.05).

Results: Of the 147 patients, 41 (27.9%) presented with movement disorders. The most frequent syndromes were normal pressure hydrocephalus (NPH) (n=14; 34.1%) and parkinsonism (n=13; 31.7%), followed by corticobasal syndrome (CBS) (n=4; 9.8%), dystonia (n=2; 4.9%), chorea (n=1; 2.4%), and cerebellar ataxia (n=1; 2.4%). Nonspecific gait disturbance was observed in 20 patients (48.8%). According to the ATN 2018 biomarker classification, 8 patients (19.5%) exhibited a biomarker profile consistent with AD, while 33 (80.5%) were classified as non-AD. At the time of this cohort analysis, clinical diagnoses were heterogeneous, most commonly including normal pressure hydrocephalus–related syndromes, parkinsonian disorders, corticobasal syndrome, and mixed or vascular dementias.

Conclusion: Movement disorders were identified in 27.9% of patients referred for cognitive evaluation, of whom 8 (19.5%) showed an AT(N) biomarker profile consistent with AD. Motor features are recognized in atypical AD presentations, particularly within the corticobasal syndrome spectrum, where AD pathology may account for 15–50% of biomarker-positive cases (1,2). These findings highlight the value of CSF biomarkers for etiological differentiation of neurodegenerative disorders (5–7).

References: 1. Graff-Radford J, Yong KXX, Apostolova LG, et al. New insights into atypical Alzheimer’s disease in the era of biomarkers. Lancet Neurology. 2021;20(3):222–234.
2. Dubois B, Villain N, Schneider L, et al. Alzheimer disease as a clinical-biological construct: an International Working Group recommendation. JAMA Neurology. 2024;81(1):1–12.
3. Shir D, Pham NTT, Botha H, et al. Clinicoradiologic and neuropathologic evaluation of corticobasal syndrome. Neurology. 2023;100(4):e364–e376.
4. Garcia-Cordero I, Anastassiadis C, Khoja A, et al. Evaluating the effect of Alzheimer’s disease–related biomarker change in corticobasal syndrome and progressive supranuclear palsy. Annals of Neurology. 2024;95(1):78–92.
5. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–1590.
6. Benvenutto A, Guedj E, Felician O, et al. Clinical phenotypes in corticobasal syndrome with or without amyloidosis biomarkers. Journal of Alzheimer’s Disease. 2020;74(2):497–508.
7. Palleis C, Bernhardt AM, Weidinger E, et al. A biomarker-based classification of corticobasal syndrome. Movement Disorders. 2025.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/movement-disorders-as-an-atypical-presentation-of-alzheimers-disease-a-cerebrospinal-fluid-biomarker-based-study/