Mar 17, 2020

The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5×FAD APP/PS1 Mouse Model

bioRxiv
Kelly H. ForestRobert Nichols

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the aging population. Evidence implicates elevated soluble oligomeric Aβ as one of the primary triggers during the prodromic phase leading to AD, effected largely via hyperphosphorylation of the microtubule-associated protein tau. At low, physiological levels (pM-nM), however, oligomeric Aβ has been found to regulate synaptic plasticity as a neuromodulator. Through mutational analysis, we found a core hexapeptide sequence within the N-terminal domain of Aβ(N-Aβcore) accounting for its physiological activity, and subsequently found that the N-Aβcore peptide is neuroprotective. Here, we characterized the neuroprotective potential of the N-Aβcore against dysfunction of synaptic plasticity assessed in ex vivo hippocampal slices from 5×FAD APP/PS1 mice, specifically hippocampal long-term potentiation (LTP) and long-term depression (LTD). The N-Aβcore was shown to reverse impairment in synaptic plasticity in hippocampal slices from 5×FAD APP/PS1 model mice, both for LTP and LTD. The reversal by the N-Aβcore correlated with alleviation of downregulation of hippocampal AMPA-type glutamate receptors in preparations from 5×FAD mice. The action of the N-Aβcore depended upon ...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

4-fluoroandrostenedione
Down-Regulation
Neuromodulators
Hexapeptide 4
FRAP1 protein, human
Long Term Depression
Neuroprotective Agents
1-Phosphatidylinositol 3-Kinase
Neuronal Plasticity
Mouse Model

Related Feeds

Age-related Dementia

Age-related dementia (Alzheimer's disease) results from the destructive impact of the pulse on cerebral vasculature. Evidence is reviewed that the neuropathology of the dementia is caused by the breakdown of small cerebral vessels (silent microbleeds), that the microbleeds result from pulse-induced damage to the cerebral vessels, and that pulse becomes increasingly destructive with age, because of the age-related stiffening of the aorta and great arteries, which causes an increase in the intensity of the pressure pulse. Discover the latest research on age-related dementia here.

Alzheimer's Disease: Genes&Microglia (Preprints)

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest preprints pertaining to this disease.

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Cell Aging (Preprints)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Aging Epidemiology

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Aging Epidemiology

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Cell Aging

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Alzheimer's Disease: Animal models

Alzheimer's disease is a chronic neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.