Linking Sleep Dysfunction to Tau-related Degeneration across AD Progression

将睡眠功能障碍与 AD 进展过程中 Tau 蛋白相关的退化联系起来

基本信息

项目摘要

PROJECT SUMMARY / ABSTRACT (from parent award) Sleep and circadian disturbances occur often and even precede the onset of cognitive decline, in Alzheimer' disease (AD) and other neurodegenerative diseases – and constitute a common reason for institutionalization. Sleep loss, particulary slow wave sleep (SWS), and sleep fragmentation, may contribute causally to AD by increasing amyloid-beta (Aβ) deposition, as described in PAR-18-497, but Aβ alone appears insufficient to explain all mechanisms and causation of AD clinical manifestations and disordered sleep. We discovered converging evidence in human sleep and neuropathological studies suggestive of a primary, novel role of tauopathy in AD-disordered sleep. In this connection, in postmortem brains of AD subjects, subcortical nuclei involved in circandian-sleep- -wake regulation are among the first to develop AD-type tau-based neurofibrillary tangles, before Aβ plaques appear. Our working hypothesis is that tau-induced degeneration of subcortical nuclei controlling 1) SWS; 2) waking-arousal; and 3) circadian timing is an early contributor to disrupted sleep- wake behavior in AD, preceding both cognitive decline and later emergence of the feedforward cycle of sleep disturbance and accelerated Aβ deposition. We propose to test if differences in sleep-wake behavior in progressive AD stages versus healthy controls vs. PSP ( a pure tauopathy more pronounced in subcortical areas) are accounted by differences in quantitative pathoanatomical measures (including numbers of total and specific neuronal population, and hp-tau burden) in nuclei involved in wake and NREM sleep regulation. We are uniquely poised to suceed due to our access to large longitudinal cohorts of AD and PSP patients and similarly-aged controls and successful autopsy program, expertise in p-tau and Aβ PET imaging, deep experience in clinical sleep studies in neurodegenerative disorders, tissue collections of aged controls, cases encompassing all-AD spectrum and other tauopathies, enabling stereology of whole brain regions, experience in human subcortical pathoanatomy, and cutting-edge neuropathological methods and brain network approach. This combination of factors create a unique opportunity to exploit novel human findings that will inform and complement mechanistic hypotheses and testing in model systems. This is critical, because animals' sleep- wake patterns and AD-like models diverge from those of humans and experimental models rather mimic non- AD tauopathies than tau-related AD patterns. We anticipate our findings will inform critical information on the temporal sequence of disrupted sleep and/or circadian rhythms and the accumulation and spreading of protein aggregates such as p-t and Aβ in AD. Beyond this, results from this study will inform rational therapies for treating disturbed sleep in AD.
项目摘要/摘要(来自家长奖)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Lea Tenenholz Grinberg其他文献

Hypertension may associate with cerebral small vessel disease and infarcts through the pathway of intracranial atherosclerosis
  • DOI:
    10.1016/j.neurobiolaging.2024.11.001
  • 发表时间:
    2025-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Marcelo Kenzo Naya Takahashi;Regina Silva Paradela;Lea Tenenholz Grinberg;Renata Elaine Paraizo Leite;Daniela Souza Farias-Itao;Vitor Ribeiro Paes;Maria Eduarda Braga;Michel Satya Naslavsky;Mayana Zatz;Wilson Jacob-Filho;Ricardo Nitrini;Carlos Augusto Pasqualucci;Claudia Kimie Suemoto
  • 通讯作者:
    Claudia Kimie Suemoto
Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias
通过全身尸检确定神经病理学诊断的痴呆症的死因
  • DOI:
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Beatriz Astolfi Neves;Paula Villela Nunes;Roberta Diehl Rodriguez;Atmis Medeiros Haidar;Renata Elaine Paraizo Leite;C. Nascimento;Carlos Augusto Pasqualucci;R. Nitrini;W. Jacob;B. Lafer;Lea Tenenholz Grinberg;Claudia Kimie Suemoto
  • 通讯作者:
    Claudia Kimie Suemoto

Lea Tenenholz Grinberg的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Lea Tenenholz Grinberg', 18)}}的其他基金

Imaging brain iron and protein aggregation with MRI for assessing Alzheimer's disease pathology and progression
使用 MRI 对脑铁和蛋白质聚集进行成像,以评估阿尔茨海默病的病理学和进展
  • 批准号:
    10563181
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
Imaging brain iron and protein aggregation with MRI for assessing Alzheimer's disease pathology and progression
使用 MRI 对脑铁和蛋白质聚集进行成像,以评估阿尔茨海默病的病理学和进展
  • 批准号:
    10331335
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
Core C: Human Tissue Validation
核心 C:人体组织验证
  • 批准号:
    10295515
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
Better memory with literacy acquisition later in life: a randomized controlled trial
晚年读写能力提高记忆力:一项随机对照试验
  • 批准号:
    10054007
  • 财政年份:
    2020
  • 资助金额:
    $ 1.38万
  • 项目类别:
Better memory with literacy acquisition later in life: a randomized controlled trial
晚年读写能力提高记忆力:一项随机对照试验
  • 批准号:
    10263225
  • 财政年份:
    2020
  • 资助金额:
    $ 1.38万
  • 项目类别:
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSP
阿尔茨海默病和 PSP 睡眠觉醒行为的临床特征和神经病理学基础
  • 批准号:
    10112791
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:
Linking Sleep Dysfunction to Tau-related Degeneration across AD Progression
将睡眠功能障碍与 AD 进展过程中 Tau 蛋白相关的退化联系起来
  • 批准号:
    10636812
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:
Linking Sleep Dysfunction to Tau-related Degeneration across AD Progression
将睡眠功能障碍与 AD 进展过程中 Tau 蛋白相关的退化联系起来
  • 批准号:
    10441484
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:
Linking Sleep Dysfunction to Tau-related Degeneration across AD Progression
将睡眠功能障碍与 AD 进展过程中 Tau 蛋白相关的退化联系起来
  • 批准号:
    9803439
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSP
阿尔茨海默病和 PSP 睡眠觉醒行为的临床特征和神经病理学基础
  • 批准号:
    10589765
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:

相似国自然基金

新型F-18标记香豆素衍生物PET探针的研制及靶向Alzheimer's Disease 斑块显像研究
  • 批准号:
    81000622
  • 批准年份:
    2010
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
阿尔茨海默病(Alzheimer's disease,AD)动物模型构建的分子机理研究
  • 批准号:
    31060293
  • 批准年份:
    2010
  • 资助金额:
    26.0 万元
  • 项目类别:
    地区科学基金项目
跨膜转运蛋白21(TMP21)对引起阿尔茨海默病(Alzheimer'S Disease)的γ分泌酶的作用研究
  • 批准号:
    30960334
  • 批准年份:
    2009
  • 资助金额:
    22.0 万元
  • 项目类别:
    地区科学基金项目

相似海外基金

Pathophysiological mechanisms of hypoperfusion in mouse models of Alzheimer?s disease and small vessel disease
阿尔茨海默病和小血管疾病小鼠模型低灌注的病理生理机制
  • 批准号:
    10657993
  • 财政年份:
    2023
  • 资助金额:
    $ 1.38万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10381163
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10531959
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10700991
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
Interneurons as early drivers of Huntington´s disease progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10518582
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
Interneurons as Early Drivers of Huntington´s Disease Progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10672973
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10585925
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
Oligodendrocyte heterogeneity in Alzheimer' s disease
阿尔茨海默病中的少突胶质细胞异质性
  • 批准号:
    10180000
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
Serum proteome analysis of Alzheimer´s disease in a population-based longitudinal cohort study - the AGES Reykjavik study
基于人群的纵向队列研究中阿尔茨海默病的血清蛋白质组分析 - AGES 雷克雅未克研究
  • 批准号:
    10049426
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
Repurposing drugs for Alzheimer´s disease using a reverse translational approach
使用逆翻译方法重新利用治疗阿尔茨海默病的药物
  • 批准号:
    10295809
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了