ArticleAlzheimer's research & therapy2025
Rotation errors in path integration are associated with Alzheimer's disease tau pathology: a cross-sectional study.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Path Integration in Alzheimer's Disease: Orientation, Movement, and Theta Rhythmicity.Annual review of neuroscience · 2026Review
- VR-based path integration predicts individual risk of rapid cortical decline: a one-year longitudinal study in cognitively unimpaired adults.Alzheimer's research & therapy · 2026Article
- Aberrant medial entorhinal cortex dynamics link tau pathology to spatial memory impairment.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic Profiling in Aged Mice Reveals an Association Between Sevoflurane Anesthesia and Neurocognitive Dysfunction.Cellular and molecular neurobiology · 2026Article
- Pathological tau alters head direction signaling and induces spatial disorientation.Cell reports · 2025Article
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14 authors.
Funding
Abstract
backgroundEarly Alzheimer's disease diagnosis is crucial for preventive therapy development. Standard neuropsychological evaluation does not identify clinically normal individuals with brain amyloidosis, the first stage of the pathology, defined as preclinical Alzheimer's disease. Spatial navigation assessment, in particular path integration, appears promising to detect preclinical symptoms, as the medial temporal lobe plays a key role in navigation and is the first cortical region affected by tau pathology.
methodsWe have conducted a cross-sectional study. We related the path integration performance of 102 individuals without dementia, aged over 50, to amyloid and tau pathologies, measured using positron emission tomography. We included 75 clinically normal individuals (19 with brain amyloidosis, 56 without) and 27 individuals with mild cognitive impairment (18 with brain amyloidosis, 9 without). We fitted linear mixed models to predict the path integration performances according to amyloid status or tau pathology in the medial temporal lobal, adjusting for age, gender, cognitive status, education, and video game experience. We decomposed the error into rotation and distance errors.
resultsWe observed that clinically normal adults with brain amyloidosis (preclinical Alzheimer's disease) had spatial navigation deficits when relying only on self-motion cues. However, they were able to use a landmark to reduce their errors. Individuals with mild cognitive impairment had deficits in path integration that did not improve when a landmark was added in the environment. The amyloid status did not influence performance among individuals with mild cognitive impairment. Among all individuals, rotation, but not distance, errors increased with the level of tau pathology in the medial temporal lobe.
conclusionOur results suggest that path integration performance in an environment without external cues allows identifying individuals with preclinical Alzheimer's disease, before overt episodic memory impairment is noticeable. Specifically, we demonstrated that poor angular estimation is an early cognitive marker of tau pathology, whereas distance estimation relates to older ages, not to Alzheimer's disease.
trial registrationEudra-CT 2018-003473-94.
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