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Adult hippocampal neurogenesis is impaired in patients with Alzheimer’s disease
Author(s) -
FlorGarcía Miguel,
TerrerosRoncal Julia,
MorenoJiménez Elena P,
LlorensMartin María
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047387
Subject(s) - hippocampal formation , neurogenesis , dentate gyrus , neuroscience , doublecortin , hippocampus , neun , dementia , disease , biology , psychology , medicine , pathology , immunohistochemistry
Background Alzheimer’s disease (AD) is the most common type of dementia. This devastating disease is characterized by progressive memory impairments and other behavioral alterations. The hippocampus is one of the brain areas mostly affected by AD progression. Importantly, the hippocampus hosts a unique phenomenon that occurs in the mammalian brain, namely the addition of new neurons throughout life. This process, named adult hippocampal neurogenesis (AHN), is involved in hippocampal‐dependent memory and confers an extraordinary degree of plasticity to the entire hippocampal circuitry. AHN has been extensively characterized in rodents and other mammalian species during the last decades. Determining the occurrence of AHN during physiological and pathological aging in humans has an unquestionable therapeutic potential. Method We studied AHN in a collection of post‐mortem hippocampal samples obtained from 13 neurologically healthy subjects and 45 AD patients distributed among the six neuropathological Braak stages of the disease. We quantified the presence of various sub‐populations of immature neurons in the hippocampal dentate gyrus (DG) of these subjects. Importantly, we tightly controlled tissue processing methodologies and used state‐of‐the‐art histological procedures. Result Thousands of immature neurons positive for the gold‐standard marker Doublecortin (DCX) were identified in the DG of these subjects up to the tenth decade of life. In contrast, we observed an early and sharp decrease in the number of new neurons in patients with AD. Strikingly, the number of cells further decreased as the disease progressed, even though the number of mature neurons positive for the neuronal nuclei (NeuN) remained unchanged. Accordingly, specific decrease in the ratio between immature/mature neurons was observed along the progression of the disease. Importantly, AHN impairments occurred before the generalized presence of neurofibrillary tangles or senile plaques in the DG. Conclusion Our data demonstrate the persistence of AHN during physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits that occurs in AD. Therefore, the putative detection of AHN impairments by non‐invasive techniques might turn this phenomenon into a relevant biomarker for AD progression.