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.
BroussardJI, YangK, LevineAT, TsetsenisT, JensonD, CaoF, GarciaI, ArenkielBR, ZhouF-M, De BiasiM, DaniJA (2016) Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the hippocampus. Cell Rep14, 1930–1939.
5.
TakeuchiT, DuszkiewiczAJ, SonnebornA, SpoonerPA, YamasakiM, WatanabeM, SmithCC, FernándezG, DeisserothK, GreeneRW, MorrisRGM (2016) Locus coeruleus and dopaminergic consolidation of everyday memory. Nature537, 357–362.
6.
KempadooKA, MosharovEV, ChoiSJ, SulzerD, KandelER (2016) Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory. Proc Natl Acad Sci U S A113, 14835–14840.
7.
NobiliA, LatagliataEC, ViscomiMT, CavallucciV, CutuliD, GiacovazzoG, KrashiaP, RizzoFR, MarinoR, FedericiM, De BartoloP, AversaD, Dell’AcquaMC, CordellaA, SancandiM, KellerF, PetrosiniL, Puglisi-AllegraS, MercuriNB, CoccurelloR, BerrettaN, D’AmelioM (2017) Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease. Nat Commun8, 14727.
8.
RussoSJ, NestlerEJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci14, 609–625.
IsmailZ, SmithEE, GedaY, SultzerD, BrodatyH, SmithG, Agüera-OrtizL, SweetR, MillerD, LyketsosCG, Neuropsychiatric Symptoms Professional Interest ISTAART, Area (2016) Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement12, 195–202.
11.
De MarcoM, VenneriA (2018) Volume and connectivity of the ventral tegmental Area are linked to neurocognitive signatures of Alzheimer’s disease in humans. J Alzheimers Dis, in press.
12.
MatherM, HarleyCW (2016) The locus coeruleus: Essential for maintaining cognitive function and the aging brain. Trends Cogn Sci20, 214–226.
13.
RorabaughJM, ChalermpalanupapT, Botz-ZappCA, FuVM, LembeckNA, CohenRM, WeinshenkerD (2017) Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer’s disease. Brain140, 3023–3038.
14.
SurmeierDJ (2007) Calcium, ageing, and neuronal vulnerability in Parkinson’s disease. Lancet Neurol6, 933–938.
15.
CaminitiSP, PresottoL, BaronciniD, GaribottoV, MorescoRM, GianolliL, VolontéMA, AntoniniA, PeraniD (2017) Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson’s disease. Neuroimage Clin14, 734–740.
16.
BraakH, AlafuzoffI, ArzbergerT, KretzschmarH, Del TrediciK (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol (Berl)112, 389–404.
