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Alzheimer's disease (AD) is a progressive neurological disorder characterized by several cognitive and non-cognitive symptoms, with episodic memory being the earliest and most prominently impaired cognitive function. Dopaminergic signals are required for encoding hippocampal memory for new events and the ventral tegmental area (VTA), together with the locus coeruleus, are the primary sources of dopamine acting on dopaminergic receptors in the hippocampus. With this in mind, a recent study on a validated mouse model of AD highlighted on the hippocampal dysfunction and its correlation with an early degeneration of dopaminergic neurons in the VTA. In this issue, De Marco and Venneri test the hypothesis that the volume of the VTA nucleus in humans might be associated with cognitive features of AD. [ABSTRACT FROM AUTHOR]

Amyloid-β protein precursor (AβPP) is a ubiquitous protein found in all cell types, suggesting basic and yet important roles, which still remain to be fully elucidated. Loss of function of AβPP has been linked to abnormal neuronal morphology and synaptic function within the hippocampus and alterations in spatial learning, suggesting a neurotrophic role for this protein. Besides AβPP, nerve growth factor (NGF) and other neurotrophins have also been shown to finely modulate neuronal excitability, synaptic plasticity, and cognitive functions. In addition, recent data support the hypothesis of a functional interconnection between AβPP and NGF pathway. Here, we demonstrated that loss of AβPP function, leading to progressive decrease of choline acetyltransferase expression in the septum, correlates with age-related impairment of long-term potentiation (LTP) in the dentate gyrus. We next addressed whether impaired hippocampal plasticity in AβPP-null mice can be restored upon NGF treatment. Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in AβPP-null mice through p75NTR and JNK pathway activation. Overall the present study may unveil a new mechanism by which, in the absence of AβPP, NGF treatment may preferentially direct p75-neurotrophin-dependent JNK activation toward regeneration and plasticity in functionally relevant brain circuits. [ABSTRACT FROM AUTHOR]

Amyloid-β protein precursor (AβPP) is a ubiquitous protein found in all cell types, suggesting basic and yet important roles, which still remain to be fully elucidated. Loss of function of AβPP has been linked to abnormal neuronal morphology and synaptic function within the hippocampus and alterations in spatial learning, suggesting a neurotrophic role for this protein. Besides AβPP, nerve growth factor (NGF) and other neurotrophins have also been shown to finely modulate neuronal excitability, synaptic plasticity, and cognitive functions. In addition, recent data support the hypothesis of a functional interconnection between AβPP and NGF pathway. Here, we demonstrated that loss of AβPP function, leading to progressive decrease of choline acetyltransferase expression in the septum, correlates with age-related impairment of long-term potentiation (LTP) in the dentate gyrus. We next addressed whether impaired hippocampal plasticity in AβPP-null mice can be restored upon NGF treatment. Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in AβPP-null mice through p75NTR and JNK pathway activation. Overall the present study may unveil a new mechanism by which, in the absence of AβPP, NGF treatment may preferentially direct p75-neurotrophin-dependent JNK activation toward regeneration and plasticity in functionally relevant brain circuits. [ABSTRACT FROM AUTHOR]

Amyloid-β protein precursor (AβPP) is a ubiquitous protein found in all cell types, suggesting basic and yet important roles, which still remain to be fully elucidated. Loss of function of AβPP has been linked to abnormal neuronal morphology and synaptic function within the hippocampus and alterations in spatial learning, suggesting a neurotrophic role for this protein. Besides AβPP, nerve growth factor (NGF) and other neurotrophins have also been shown to finely modulate neuronal excitability, synaptic plasticity, and cognitive functions. In addition, recent data support the hypothesis of a functional interconnection between AβPP and NGF pathway. Here, we demonstrated that loss of AβPP function, leading to progressive decrease of choline acetyltransferase expression in the septum, correlates with age-related impairment of long-term potentiation (LTP) in the dentate gyrus. We next addressed whether impaired hippocampal plasticity in AβPP-null mice can be restored upon NGF treatment. Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in AβPP-null mice through p75NTR and JNK pathway activation. Overall the present study may unveil a new mechanism by which, in the absence of AβPP, NGF treatment may preferentially direct p75-neurotrophin-dependent JNK activation toward regeneration and plasticity in functionally relevant brain circuits.