Suspecting Non-Alzheimer’s Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images

Malotaux, Vincent; Colmant, Lise; Quenon, Lisa; Huyghe, Lara; Gérard, Thomas; Dricot, Laurence; Ivanoiu, Adrian; Lhommel, Renaud; Hanseeuw, Bernard

doi:10.3233/jad-230696

Cited by 2 publications

References 44 publications

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Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans

Budak,

Fausto,

Osiecka

et al. 2024

Alz Res Therapy

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Background Phosphorylated tau (p-tau) and amyloid beta (Aβ) in human plasma may provide an affordable and minimally invasive method to evaluate Alzheimer’s disease (AD) pathophysiology. The medial temporal lobe (MTL) is susceptible to changes in structural integrity that are indicative of the disease progression. Among healthy adults, higher dynamic network flexibility within the MTL was shown to mediate better generalization of prior learning, a measure which has been demonstrated to predict cognitive decline and neural changes in preclinical AD longitudinally. Recent developments in cognitive, neural, and blood-based biomarkers of AD risk that may correspond with MTL changes. However, there is no comprehensive study on how these generalization biomarkers, long-term memory, MTL dynamic network flexibility, and plasma biomarkers are interrelated. This study investigated (1) the relationship between long-term memory, generalization performance, and MTL dynamic network flexibility and (2) how plasma p-tau231, p-tau181, and Aβ42/Aβ40 influence generalization, long-term memory, and MTL dynamics in cognitively unimpaired older African Americans. Methods 148 participants (Meanage: 70.88,SDage: 6.05) were drawn from the ongoing longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University–Newark. Cognition was evaluated with the Rutgers Acquired Equivalence Task (generalization task) and Rey Auditory Learning Test (RAVLT) delayed recall. MTL dynamic network connectivity was measured from functional Magnetic Resonance Imaging data. Plasma p-tau231, p-tau181, and Aβ42/Aβ40 were measured from blood samples. Results There was a significant positive correlation between generalization performance and MTL Dynamic Network Flexibility (t = 3.372, β = 0.280, p < 0.001). There were significant negative correlations between generalization performance and plasma p-tau231 (t = -3.324, β = -0.265, p = 0.001) and p-tau181 (t = -2.408, β = -0.192, p = 0.017). A significant negative correlation was found between plasma p-tau231 and MTL Dynamic Network Flexibility (t = -2.825, β = -0.232, p = 0.005). Conclusions Increased levels of p-tau231 are associated with impaired generalization abilities and reduced dynamic network flexibility within the MTL. Plasma p-tau231 may serve as a potential biomarker for assessing cognitive decline and neural changes in cognitively unimpaired older African Americans.

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Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans

Budak,

Fausto,

Osiecka

et al. 2024

Alz Res Therapy

View full text Add to dashboard Cite

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Rotation errors in path integration indicate Alzheimer’s disease tau pathology: a cross-sectional study

Colmant,

Quenon,

Huyghe

et al. 2024

Preprint

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Background Early 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. Methods We 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 73 clinically normal individuals (18 with brain amyloidosis, 55 without) and 29 individuals with mild cognitive impairment (19 with brain amyloidosis, 10 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. Results We 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, error increased with the level of tau pathology in the medial temporal lobe. Conclusion Our 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 registration: Eudra-CT 2018-003473-94

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Suspecting Non-Alzheimer’s Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images

Cited by 2 publications

References 44 publications

Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans

Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans

Rotation errors in path integration indicate Alzheimer’s disease tau pathology: a cross-sectional study

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