AQP4-dependent enhancement of glymphatic function attenuates tau pathology and neurodegeneration in PS19 mice.
Authors: Yamada K, Ishida K, Sakamoto A, Shimada H, Watanabe M, Shimojo M, Igarashi H, Iwatsubo T
Journal: Molecular neurodegeneration
mental health
psychology
open access
Abstract
Alzheimer’s disease (AD) is a progressive
neurodegenerative
disorder that significantly affects the aging population. As the leading cause of dementia, AD accounts
for 60–80% of all dementia cases worldwide. Globally,
over 55 million people are estimated to be living with dementia, a
figure projected to nearly triple by 2050 due to demographic aging
and a lack of curative therapies. Clinically,
AD begins with subtle symptoms such as episodic memory loss and impaired
spatial navigation, progressing insidiously to involve deficits in
executive function, language, behavior, and eventually, total independence. In its later stages, patients may experience severe neuropsychiatric
symptoms, such as hallucinations, delusions, depression, and sleep
problems, which further exacerbate caregiver burden. Pathologically, AD is characterized by the extracellular
accumulation
of amyloid-β (Aβ) peptides forming diffuse and neuritic
plaques, and the intracellular aggregation of neurofibrillary tangles
(NFTs) composed of hyperphosphorylated tau proteins. These lesions are predominantly distributed in the hippocampus,
entorhinal cortex, and neocortical association areas, regions essential
for memory and cognition, and are associated with synaptic loss, neuronal
atrophy, and widespread neurodegeneration. In addition to these hallmark features, AD pathogenesis encompasses
a spectrum of molecular abnormalities, including chronic neuroinflammation,
oxidative stress, mitochondrial dysfunction, and blood–brain
barrier (BBB) breakdown, all of which synergistically contribute to
disease progression (). While the neuropathological features of AD are well characterized,
the mechanisms underlying disease initiation and progression remain
under investigation. Overview of AD pathology. AD is characterized by multiple
interrelated
pathological hallmarks, including amyloid plaque accumulation, tau
hyperphosphorylation, cerebrovascular impairment, cholinergic neuron
loss, neuroinflammation, and mitochondrial dysfunction.
neurodegenerative
disorder that significantly affects the aging population. As the leading cause of dementia, AD accounts
for 60–80% of all dementia cases worldwide. Globally,
over 55 million people are estimated to be living with dementia, a
figure projected to nearly triple by 2050 due to demographic aging
and a lack of curative therapies. Clinically,
AD begins with subtle symptoms such as episodic memory loss and impaired
spatial navigation, progressing insidiously to involve deficits in
executive function, language, behavior, and eventually, total independence. In its later stages, patients may experience severe neuropsychiatric
symptoms, such as hallucinations, delusions, depression, and sleep
problems, which further exacerbate caregiver burden. Pathologically, AD is characterized by the extracellular
accumulation
of amyloid-β (Aβ) peptides forming diffuse and neuritic
plaques, and the intracellular aggregation of neurofibrillary tangles
(NFTs) composed of hyperphosphorylated tau proteins. These lesions are predominantly distributed in the hippocampus,
entorhinal cortex, and neocortical association areas, regions essential
for memory and cognition, and are associated with synaptic loss, neuronal
atrophy, and widespread neurodegeneration. In addition to these hallmark features, AD pathogenesis encompasses
a spectrum of molecular abnormalities, including chronic neuroinflammation,
oxidative stress, mitochondrial dysfunction, and blood–brain
barrier (BBB) breakdown, all of which synergistically contribute to
disease progression (). While the neuropathological features of AD are well characterized,
the mechanisms underlying disease initiation and progression remain
under investigation. Overview of AD pathology. AD is characterized by multiple
interrelated
pathological hallmarks, including amyloid plaque accumulation, tau
hyperphosphorylation, cerebrovascular impairment, cholinergic neuron
loss, neuroinflammation, and mitochondrial dysfunction.