Abstract—Human acidic fibroblast growth factor (haFGF), aneurotrophin-like growth factor in the brain, plays importantroles in the development, differentiation and regenerationof brain neurons, which makes it potential to treatAlzheimer’s disease (AD). In this study, haFGF14–154 andTAT-haFGF14–154 (haFGF14–154 fused with the cell-penetratingpeptide transactivator of transcription protein transductiondomain (TAT-PTD)) were intranasally administrated for5 weeks to investigate the effects on senescence-acceleratedmouse prone-8 (SAMP8) mice (a mouse model of AD).Results showed that TAT-PTD could increase the concentrationof haFGF in the brain significantly, and TAT-haFGF14–154was more effective than haFGF14–154 in the same dosage(300lg/kg).Importantly,TAThaFGF14154improved thelearning and memory abilities of SAMP8 mice in the behavioraltest, and promoted thefunctionofcholinergicsystemby measuring the relevant biomarkers (acetylcholine (ACh)level, acetylcholinesterase (AChE)andcholineacetyltransferase
(ChAT) activities). TAT-haFGF14–154 also significantlyreduced b-amyloid protein1–42 (Ab1–42) deposits as well as
the levels of Ab soluble forms in the mice brains and preventedthe neurons from apoptosis. Besides, the oxidative
stress impairment in the brain and serum was also ameliorated.The results suggest that TAT-haFGF14–154 couldattenuatethe disease progression of SAMP8 AD mice, and themechanism is related to the regulation of neurons microenvironment