B -Amyloid (A )-targeting liposomes (LIP) with surface serotoninmodulator(SM) and apolipoprotein E (ApoE) wereutilized to deliver nerve growth factor (NGF) across the blood–brain barrier (BBB) for neuroprotectionin the hippocampus. An in vitro Alzheimer‟s disease(AD) model of degenerated SK-N-MC cellsand anin vivo AD model of Aβ-insulted Wistar rats wereused to assess the therapeutic efficacy ofSM- and ApoE-grafted LIPcarrying NGF (NGF-SM-ApoE-LIP). The experimental evidence revealed that the modified SM and ApoEon the surface of LIPincreased the permeation of NGF across the BBBwithout a serious damage to structural integrity of the tight junction. When compared with free NGF, NGF-SM-ApoE-LIP upregulatedthe expression of phosphorylatedneurotrophic tyrosine kinase receptor type 1on cholinergic neurons and significantly improved their survival. In the brain of rats, NGF-SM-ApoE-LIP could reduce the secretion of acetylcholinesteraseand malondialdehydeand rescuehippocampal neurons from apoptosis. The synergisticeffect of SM andApoE in the current LIP carriers is effective in the induction of NGF to inhibit the neurotoxicityof Aβ and can be a potent anti-apoptotic pharmacotherapyforAD care. Keywords: Alzheimer‟s disease; blood–brain barrier; serotoninmodulator;apolipoprotein E; nerve growth factor;liposome