Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination DOI Creative Commons
Casey R. Vanderlip, Lisa Taylor, Soyun Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 26, 2024

Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes subtle memory deficits observed during the preclinical stage. The heterogenous emergence deposition may selectively impact certain domains, which rely on distinct underlying neural circuits. In this context, we tested specific domains mnemonic discrimination, computation essential for episodic memory, exhibit related early deposition. We 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (Aβ-PET), and control group 35 young adults, suite discrimination tasks taxing object, spatial, temporal domains. hypothesized that would be associated with performance due Aβ's propensity accumulate in basal frontotemporal cortex, supports processing. Consistent hypothesis, found dissociation generalized age-related were object spatial while Aβ-PET levels discrimination. Further, higher medial orbitofrontal inferior regions supporting processing, greater deficits, pointing selective vulnerability circuits processing AD progression. These results suggest accumulation within disrupt AD, serve as sensitive behavioral biomarker emerging

Язык: Английский

Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer’s spectrum DOI Creative Commons
Casey R. Vanderlip, Craig E.L. Stark

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 26, 2024

Abstract Digital cognitive assessments, particularly those that can be done at home, present as low burden biomarkers for participants and patients alike, but their effectiveness in diagnosis of Alzheimer’s or predicting its trajectory is still unclear. Here, we assessed what utility added value these digital assessments provide identifying high risk decline. We analyzed >500 ADNI who underwent a brief assessment Aβ/tau PET scans, examining ability to distinguish status predict Performance on the were superior both cortical Aβ entorhinal tau detecting mild impairment future decline, with mnemonic discrimination deficits emerging most critical measure decline accumulation. are effective at-risk individuals, supporting low-burden tools early detection monitoring.

Язык: Английский

Процитировано

4
Integrating Plasma pTau-217 and Digital Cognitive Assessments for Early Detection in Alzheimer’s Disease DOI Creative Commons
Casey R. Vanderlip, Craig E.L. Stark

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Plasma pTau-217 has emerged as a sensitive and specific biomarker for early Alzheimer’s disease detection. However, the timeline of pathological changes onset cognitive decline remain unclear. On other hand, digital assessments have also shown promise in detecting subtle changes, but sensitivity specificity these is not fully understood. Here, we investigate whether combining low-burden tools can improve identification cognitively unimpaired individuals at high risk future decline. We analyzed 954 amyloid-positive who completed brief assessment blood test pTau-217, evaluating their ability to identify those on Preclinical Cognitive Composite (PACC) Mini-Mental State Exam (MMSE). Further, investigated predictive value measures differed by sex or APOE status. found that memory performance with enhanced declined PACC MMSE over next five years, even after controlling age, sex, education, baseline performance. Specifically, both elevated low were greater than either factor alone. Notably, did differ was significantly stronger APOE4 noncarriers compared carriers. Together, this suggests plasma provides reliable method identifying disease.

Язык: Английский

Процитировано

0
Misclassification in memory modification in AppNL-G-F knock-in mouse model of Alzheimer’s disease DOI Open Access

Marilyn Huang,

Yusuke Suzuki, Hiroki Sasaguri

и другие.

Опубликована: Март 31, 2025

Alzheimer’s disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in AD continuum. Computational modeling is a promising approach explain generative process underlying behavioral with number putative variables. Nonetheless, internal models patient’s reasoning remain underexplored AD. Determining states an model between measurable pathological phenotypes would advance explanations about earlier stages beyond assessing behavior alone. In this study, we assumed latent as estimated defined by parameters being conjunction phenotypes. The 6- 12-month-old App NL-G-F knock-in mice age-matched control underwent memory modification learning, which consisted classical fear conditioning, extinction, reinstatement. results showed that exhibited lower extent reinstatement memory. revealed deficit due their biased toward overgeneralization or overdifferentiation observations, consequently competing memories were not retained. This was replicated another type learning reversal Barnes maze task. Following mice, given spatial cues, failed infer coexisting for two goal locations during trial. We concluded altered illustrated misclassification process. novel highlights potential investigating precisely multidimensionally evaluate how interventions may work.

Язык: Английский

Процитировано

0
Misclassification in memory modification in AppNL-G-F knock-in mouse model of Alzheimer’s disease DOI Open Access

Marilyn Huang,

Yusuke Suzuki, Hiroki Sasaguri

и другие.

Опубликована: Март 31, 2025

Alzheimer’s disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in AD continuum. Computational modeling is a promising approach explain generative process underlying behavioral with number putative variables. Nonetheless, internal models patient’s reasoning remain underexplored AD. Determining states an model between measurable pathological phenotypes would advance explanations about earlier stages beyond assessing behavior alone. In this study, we assumed latent as estimated defined by parameters being conjunction phenotypes. The 6- 12-month-old App NL-G-F knock-in mice age-matched control underwent memory modification learning, which consisted classical fear conditioning, extinction, reinstatement. results showed that exhibited lower extent reinstatement memory. revealed deficit due their biased toward overgeneralization or overdifferentiation observations, consequently competing memories were not retained. This was replicated another type learning reversal Barnes maze task. Following mice, given spatial cues, failed infer coexisting for two goal locations during trial. We concluded altered illustrated misclassification process. novel highlights potential investigating precisely multidimensionally evaluate how interventions may work.

Язык: Английский

Процитировано

0
APOE4 Increases Susceptibility to Amyloid, Accelerating Episodic Memory Decline DOI Creative Commons
Casey R. Vanderlip, Craig E.L. Stark

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Individuals with one copy of APOE4 exhibit greater amyloid-beta (Aβ) deposition compared to noncarriers, an effect that even more pronounced in homozygotes. Interestingly, carriers not only show AD pathology but also experience rapid cognitive decline, particularly episodic memory. The underlying mechanisms driving this domain-specific vulnerability, however, remain unclear. In study, we examined whether accelerated decline memory among due increased Aβ or heightened susceptibility Aβ-related effects. Using data from Disease Research Initiative, modeled amyloid duration, estimated number years individual has been amyloid-positive, and its impact on trajectories. Our findings reveal associated as a function duration. This was dose-dependent, homozygotes declining rapidly than heterozygotes, it consistently observed across multiple tasks measures. Importantly, pattern other domains, such processing speed, executive function, visuospatial skills, language, crystallized intelligence. These results suggest trajectories differ by APOE genotype, conferring vulnerability hippocampal dysfunction early course. Future research should investigate these differences stem distinct pathological cascades carriers.

Язык: Английский

Процитировано

1
Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination DOI Creative Commons
Casey R. Vanderlip, Lisa Taylor, Soyun Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 26, 2024

Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes subtle memory deficits observed during the preclinical stage. The heterogenous emergence deposition may selectively impact certain domains, which rely on distinct underlying neural circuits. In this context, we tested specific domains mnemonic discrimination, computation essential for episodic memory, exhibit related early deposition. We 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (Aβ-PET), and control group 35 young adults, suite discrimination tasks taxing object, spatial, temporal domains. hypothesized that would be associated with performance due Aβ's propensity accumulate in basal frontotemporal cortex, supports processing. Consistent hypothesis, found dissociation generalized age-related were object spatial while Aβ-PET levels discrimination. Further, higher medial orbitofrontal inferior regions supporting processing, greater deficits, pointing selective vulnerability circuits processing AD progression. These results suggest accumulation within disrupt AD, serve as sensitive behavioral biomarker emerging

Язык: Английский

Процитировано

0