Abstract
Recently, we reported that ALWPs, which we developed by combining Liuwei Dihuang pills (LWPs) with antler, regulate the LPS-induced neuroinflammatory response and rescue LPS-induced short- and long-term memory impairment in wild-type (WT) mice. In the present study, we examined the effects of ALWPs on Alzheimer’s disease (AD) pathology and cognitive function in WT mice as well as 5x FAD mice (a mouse model of AD). We found that administration of ALWPs significantly reduced amyloid plaque levels in 5x FAD mice and significantly decreased amyloid β (Aβ) levels in amyloid precursor protein (APP)-overexpressing H4 cells. In addition, ALWPs administration significantly suppressed tau hyperphosphorylation in 5x FAD mice. Oral administration of ALWPs significantly improved long-term memory in scopolamine (SCO)-injected WT mice and 5x FAD mice by altering dendritic spine density. Importantly, ALWPs promoted spinogenesis in primary hippocampal neurons and WT mice and modulated the dendritic spine number in an extracellular signal-regulated kinase (ERK)-dependent manner. Taken together, our results suggest that ALWPs are a candidate therapeutic drug for AD that can modulate amyloid plaque load, tau phosphorylation, and synaptic/cognitive function.
Highlights
Alzheimer’s disease (AD) is an age-related neurodegenerative disease (Deary and Whalley, 1988; Hardy and Selkoe, 2002) with several major pathological hallmarks reflecting the disease mechanism
We initially examined whether ALWPs can alter amyloid β (Aβ) plaque levels
We examined whether dendritic spine morphology was altered in ALWPstreated 5x FAD mice and found shorter and narrow spines in apical oblique (AO) dendrites of hippocampus CA1 compared to the control group (Supplementary Figure S3)
Summary
Alzheimer’s disease (AD) is an age-related neurodegenerative disease (Deary and Whalley, 1988; Hardy and Selkoe, 2002) with several major pathological hallmarks reflecting the disease mechanism. Abnormal hyperphosphorylation of tau and accumulation of Aβ plaques can lead to dendritic spine loss, ALWPs Effect on AD Pathology synaptic dysfunction, neuronal cell death, and memory impairment (Hardy and Selkoe, 2002). Aggregation of tau causes dendritic spine loss and impairment of synaptic function by inducing the disassembly of microtubules (Thies and Mandelkow, 2007; Nisbet et al, 2015). Both Aβ and tau appear to be involved in dendritic spine loss and synaptic dysfunction, which lead to cognitive decline in AD, and drugs that can reduce both Aβ plaques and tau phosphorylation are therapeutic candidates for AD
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