Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and neurodegeneration in the hippocampus. Despite the pathological importance of the hippocampal degeneration in AD, little topographical evidence exists of impaired hippocampal connectivity in patients with AD. To investigate the anatomical connections of the hippocampus, we injected the neurotracer 1,1′-dioctadecyl-3,3,3′3,3′-tetramethyl-indocarbocyanine perchlorate (DiI) into the hippocampi of 5XFAD mice, which were used as an animal model of AD. In wild-type controls, DiI-containing cells were found in the entorhinal cortex, medial septum, locus coeruleus, dorsal raphe, substantia nigra pars compacta, and olfactory bulb. Hippocampal inputs were decreased in multiple brain regions in the 5XFAD mice compared to wild-type littermate mice. These results are the first to reveal alterations at the cellular level in hippocampal connectivity in the brains of 5XFAD mice. These results suggest that anatomical mapping of hippocampal connectivity will elucidate new pathogenic mechanisms and therapeutic targets for AD treatment.
Highlights
Alzheimer’s disease (AD), which is the most divesting agedependent neurodegenerative disorder, is characterized by memory and cognition impairments
Fluorescent cells were prominent in specific brain regions or nuclei, including the medial septum (MS), locus coeruleus (LC), dorsal raphe (DR), substantia nigra pars compacta (SNc), and olfactory bulb (OB), in the DiI-injected littermate controls (Fig. 2a–h)
Due to the critical role of the hippocampus in cognitive functions, hippocampal connectivity has been examined in the brains of patients with AD
Summary
Alzheimer’s disease (AD), which is the most divesting agedependent neurodegenerative disorder, is characterized by memory and cognition impairments. Patients with damaged hippocampi show impaired declarative and semantic memory [5, 6]. Hippocampal degeneration, which is the most obvious feature of patients with AD, results in symptoms of deteriorating cognitive functions, olfactory impairments, and emotional deficits [7,8,9]. The neuronal pathways from the EC to the hippocampus are indispensable for cognitive functions, including memory retrieval and initial memory acquisition [11]. The olfacto-hippocampal network has a critical role in odor-discrimination learning [12], and a correlation has been reported between olfactory deficits and cognitive function in AD patients [13,14,15,16].
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