Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease

Michael H. Donovan, Umar Yazdani, Rebekah D. Norris, Dora Games, Dwight C. German, Amelia J. Eisch

Research output: Contribution to journalArticle

275 Citations (Scopus)

Abstract

Abnormal subgranular zone (SGZ) neurogenesis is proposed to contribute to Alzheimer's disease (AD)-related decreases in hippocampal function. Our goal was to examine hippocampal neurogenesis in the PDAPP mouse, a model of AD with age-dependent accumulation of amyloid-β42 (Aβ42) -containing plaques that is well studied with regard to AD therapies. A secondary goal was to determine whether altered neurogenesis in the PDAPP mouse is associated with abnormal maturation or number of mature cells. A tertiary goal was to provide insight into why hippocampal neurogenesis appears to be increased in AD post-mortem tissue and decreased in most AD mouse models. We report an age-dependent decrease in SGZ proliferation in homozygous PDAPP mice. At 1 year of age, PDAPP mice also had new dentate gyrus granule neurons with abnormal maturation and fewer dying cells relative to control mice. In contrast to decreased SGZ cell birth, PDAPP mice had increased birth of immature neurons in the outer portion of the granule cell layer (oGCL), providing insight into why some studies link AD with increased neurogenesis. However, these ectopic oGCL cells were still rare compared with SGZ proliferating cells, emphasizing that the primary characteristic of PDAPP mice is decreased neurogenesis. The decrease in SGZ neurogenesis was not associated with an age-dependent loss of dentate granule neurons. The altered neurogenesis in the PDAPP mouse may contribute to the age-related cognitive deficits reported in this model of AD and may be a useful adjunct target for assessing the impact of AD therapies.

Original languageEnglish (US)
Pages (from-to)70-83
Number of pages14
JournalJournal of Comparative Neurology
Volume495
Issue number1
DOIs
StatePublished - Mar 1 2006

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Neurogenesis
Alzheimer Disease
Neurons
Parturition
Dentate Gyrus
Amyloid
Cell Count
Therapeutics

Keywords

  • BrdU
  • Doublecortin
  • Stereology
  • Subgranular zone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. / Donovan, Michael H.; Yazdani, Umar; Norris, Rebekah D.; Games, Dora; German, Dwight C.; Eisch, Amelia J.

In: Journal of Comparative Neurology, Vol. 495, No. 1, 01.03.2006, p. 70-83.

Research output: Contribution to journalArticle

Donovan, Michael H. ; Yazdani, Umar ; Norris, Rebekah D. ; Games, Dora ; German, Dwight C. ; Eisch, Amelia J. / Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. In: Journal of Comparative Neurology. 2006 ; Vol. 495, No. 1. pp. 70-83.
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