Research square · 2026
Basal forebrain parvalbumin neuron dysfunction links network oscillation deficits to hippocampal pathology in Alzheimer's disease.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Hwang Eunjin, Shim Hyun Soo, Kim Seung Chan, Nam Min-Ho, Hyeon Seung Jae, Kim Hea-Jin, Kim Ji Eun, Park Hyeok Ju, Woo Jiwan, Hwang Eun Mi, Stein Thor, Lee Junghee, Choi Jee Hyun, Ryu Hoon
Аннотация
BACKGROUND: Basal forebrain (BF) degeneration is a key pathological feature of Alzheimer's disease (AD) and is closely associated with cognitive decline. Although parvalbumin (PV)-expressing neurons are abundant in the BF and are important regulators of cortical network activity, their contribution to AD pathogenesis remains poorly understood.
METHODS: To investigate the role of BF-PV neurons in AD, we examined the effects of PV knockdown in the BF of APP/PS1 mice. Electrophysiological recordings, behavioral analyses, retrograde tracing, hippocampal transcriptome profiling, and integrative computational analyses, including meta-correlation analysis and artificial neural network (ANN) modeling, were performed to assess the impact of BF-PV loss on neural network activity, hippocampal pathology, and cognitive function.
RESULTS: BF-PV knockdown disrupted theta oscillations and theta-gamma coupling in the parietal cortex and impaired hippocampal synaptic activity and memory-related behaviors in mice. Retrograde tracing demonstrated that BF neuronal circuits project directly to the hippocampus. Transcriptome analysis revealed that BF-PV knockdown increased amyloidosis- and microvessel-associated gene signatures while reducing synaptic plasticity-related gene expression in the hippocampus. Furthermore, meta-correlation analyses and ANN modeling indicated that BF-PV dysfunction strongly predicts hippocampal pathology, disrupted EEG coupling, and behavioral abnormalities in AD mice.
CONCLUSIONS: These findings identify BF-PV neuronal dysfunction as an important contributor to hippocampal pathology, neural network dysregulation, and cognitive impairment in AD, highlighting BF-PV neurons as a potential mechanistic link between BF degeneration and AD progression.
METHODS: To investigate the role of BF-PV neurons in AD, we examined the effects of PV knockdown in the BF of APP/PS1 mice. Electrophysiological recordings, behavioral analyses, retrograde tracing, hippocampal transcriptome profiling, and integrative computational analyses, including meta-correlation analysis and artificial neural network (ANN) modeling, were performed to assess the impact of BF-PV loss on neural network activity, hippocampal pathology, and cognitive function.
RESULTS: BF-PV knockdown disrupted theta oscillations and theta-gamma coupling in the parietal cortex and impaired hippocampal synaptic activity and memory-related behaviors in mice. Retrograde tracing demonstrated that BF neuronal circuits project directly to the hippocampus. Transcriptome analysis revealed that BF-PV knockdown increased amyloidosis- and microvessel-associated gene signatures while reducing synaptic plasticity-related gene expression in the hippocampus. Furthermore, meta-correlation analyses and ANN modeling indicated that BF-PV dysfunction strongly predicts hippocampal pathology, disrupted EEG coupling, and behavioral abnormalities in AD mice.
CONCLUSIONS: These findings identify BF-PV neuronal dysfunction as an important contributor to hippocampal pathology, neural network dysregulation, and cognitive impairment in AD, highlighting BF-PV neurons as a potential mechanistic link between BF degeneration and AD progression.