Impact of social relationships on Alzheimer's memory impairment: mechanistic studies

Abstract

Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss culminating in cognitive impairment that not only affects a person's living ability but also becomes a society's as well as a family's economic burden. AD is the most common form of dementia in older persons. It is expected that the number of people with AD dementia will increase dramatically in the next 30 years, projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no sufficient evidence is available to support that any medicine is able to prevent or reverse the progression of the disease. Early studies have shown that social environment, particularly social relationships, can affect one's behavior and mental health. A study analyzing the correlation between loneliness and risk of developing AD revealed that lonely persons had higher risk of AD compared with persons who were not lonely. On the other hand, it has been reported that we can prevent cognitive decline and delay the onset of AD if we keep mentally active and frequently participate in social activities. In this review, we focus on the impact of social behaviors on the progression of cognitive deficit in animal models of AD with a particular emphasis on a mechanistic scheme that explains how social isolation exacerbates cognitive impairment and how social interaction with conspecifics rescues AD patients' memory deficit.

Keywords: Alzheimer’s disease; BDNF; Cognition; Epigenetic; Hippocampus; Neurogenesis; Social isolation.

Fig. 1

Schematic diagram illustrates how social isolation exacerbates memory decline in APP/PS1 mice. We propose that social isolation increases calpain activity leading to conversion of p35 to p25. Decrease in membrane associated p35 reduces α-CaMKII synaptic distribution resulting in the synaptic removal of AMPARs

Fig. 2

Co-housing with conspecific increases spine density in hippocampal CA1 neurons of the AD mice. Representative images (a) and statistical analyses of Golgi staining (b) from the hippocampal CA1 neurons of the control, memory-unimproved and memory-improved AD mice after co-housing with conspecific. ***p < 0.001 vs. memory-unimproved

Fig. 3

Schematic diagram illustrates how co-housing reverses memory decline in APP/PS1 mice. We propose that co-housing reduces HDAC2 expression and the occupancy of HDAC2 in the promoter region of Bdnf exon IV resulting in the increased levels of acetylated histone H3K9 and H4K12. This leads to the higher transcription and translation of BDNF mRNA and protein in the hippocampus that improves memory. (Modified from reference [65])