Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis

Scott, Samuel A.; Mufson, Elliott J.; Weingartner, Jean; Skau, Kenneth A.; Crutcher, Keith A.

doi:10.1523/jneurosci.15-09-06213.1995

Cited by 255 publications

(138 citation statements)

References 53 publications

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“…Our finding of increased NGF in the hippocampus of Ts65Dn vs. 2N mice at 6 months of age suggested that decreased availability of NGF at BFCN terminals was not a factor. Hippocampal NGF mRNA or protein levels have similarly been reported as unchanged or even increased in AD patients (25,26). NGF levels are reduced in the basal forebrain as a whole (26) and specifically within BFCNs (26,27) in AD.…”

Section: Discussionmentioning

confidence: 99%

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Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Cooper

Salehi

Delcroix

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

315

312

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Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive changes in the hippocampal terminal fields of these neurons with respect to diploid controls. The changes were associated with significantly impaired retrograde transport of nerve growth factor (NGF) from the hippocampus to the basal forebrain. Intracerebroventricular NGF infusion reversed well established abnormalities in BFCN size and number and restored the deficit in cholinergic innervation. The findings are evidence that even BFCNs chronically deprived of endogenous NGF respond to an intervention that compensates for defective retrograde transport. We suggest that age-related cholinergic neurodegeneration may be a treatable disorder of failed retrograde NGF signaling.

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Section: Discussionmentioning

confidence: 99%

“…Hippocampal NGF mRNA or protein levels have similarly been reported as unchanged or even increased in AD patients (25,26). NGF levels are reduced in the basal forebrain as a whole (26) and specifically within BFCNs (26,27) in AD. Of note, we detected a trend toward decreased NGF levels in the septum of Ts65Dn mice.…”

Section: Discussionmentioning

confidence: 99%

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Cooper

Salehi

Delcroix

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

315

312

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“…choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) with a decrease of cholinergic transmission (Svendsen et al, 1991;Venero et al, 1994). In contrast, the levels of proNGF, a precursor of NGF, which is the predominant form in human and rodent brain, are doubled in frontal and occipital cortex and in hippocampus in late-stage AD (Crutcher et al, 1993;Scott et al, 1995;Narisawa-Saito et al, 1996;Hellweg et al, 1998;Hock et al, 2000;Fahnestock et al, 2001;Peng et al, 2004) and appear to be 40%-50% increased in individuals with mild cognitive impairment (MCI) (Peng et al, 2004), suggesting that an unbalance in NGF processing may contribute, and in some instances cause, the onset of AD neurodegeneration. In this regard, an unbalance of the cascade of protease complex (plasminogen/plasmin; tPA,Neuroserpin, MMP-9) leading to a deficit of proNGF/NGF has been recently reported in human AD brains (Bruno et al, 2006;Cuello and Bruno, 2007).…”

Section: Ngf and Its Receptors In Admentioning

confidence: 99%

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

Calissano

Matrone

Amadoro

2010

Developmental Neurobiology

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Converging lines of evidence on the possible connection between NGF signaling and Alzheimer's diseases (AD) are unraveling new facets which could depict this neurotrophin (NTF) in a more central role. AD animal models have provided evidence that a shortage of NGF supply may induce an AD-like syndrome. In vitro experiments, moreover, are delineating a possible temporal and causal link between APP amiloydogenic processing and altered post-translational tau modifications. After NGF signaling interruption, the pivotal upstream players of the amyloid cascade (APP, b-secretase, and active form of c-secretase) are up-regulated, leading to an increased production of amyloid b peptide (Ab) and to its intracellular aggregation in molecular species of different sizes. Contextually, the Ab released pool generates an autocrine toxic loop in the same healthy neurons. At the same time tau protein undergoes anomalous, GSKb-mediated, phosphorylation at specific pathogenetic sites (Ser262 and Thr 231), caspase(s) and calpain-I-mediated truncation, detachment from microtubules with consequent cytoskeleton collapse and axonal transport impairment. All these events are inhibited when the amyloidogenic processing is reduced by b and c secretase inhibitors or anti-Ab antibodies and appear to be causally correlated to TrkA, p75CTF, Ab, and PS1 molecular association in an Ab-mediated fashion. In this scenario, the so-called trophic action exerted by NGF (and possibly also by other neurotrophins) in these targets neurons is actually the result of an anti-amyloidogenic activity. '

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“…In addition, NGF levels are increased in cerebral cortex and decreased in nucleus basalis in Alzheimer's disease (Scott et al, 1995), suggesting that this disease could be associated with impaired TrkA-dependent retrograde transport of NGF. It is possible that the decreases in TrkA expression and retrograde transport are simply consequences of other processes that are responsible for the etiology of Alzheimer's disease.…”

Section: Alzheimer's Disease and Retrograde Transportmentioning

confidence: 99%

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Silver¹,

Fagiolini²,

Gillespie³

et al. 2001

Neuroscience

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AbstractöIntracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the e¡ects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF a¡ects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no e¡ect on the normal developmental segregation of geniculocortical a¡erents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75 NTR -, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons.We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: TrkA, p75, choline acetyltransferase, retrograde transport, acetylcholine, monocular deprivation.Monocular deprivation (MD) is a well-studied model of experience-dependent cortical plasticity. When one eye of an animal is occluded during a critical period of development, that eye loses most of its ability to drive neurons in primary visual cortex, shifting the distribution of visual responses to favor the nondeprived eye (Wiesel and Hubel, 1963). Intracerebroventricular (ICV) administration of the neurotrophin nerve growth factor (NGF) to rats during a critical period of development blocks the e¡ects of MD (Domenici et al., 1991;Ma¡ei et al., 1992). This has been demonstrated at several levels of analysis, including physiological, anatomical, immunocytochemical, and behavioral (for a review, see Cellerino and Ma¡ei, 1996). Infusion of NGF directly into developing rat visual cortex also prevents physiological ocular dominance plasticity (Lodovichi et al., 2000).In addition, anti-NGF antibodies prevent normal anatomical and physiological development of the visual system when they are administered to rats by implantation of antibody-secreting hybridoma cells in the lateral ventricle (Berardi et al., 1994). These antibodies also prolong the critical period for ocular dominance plasticity in the rat (Domenici et al., 1994a). Together, these results demonstrate an imp...

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Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis

Cited by 255 publications

References 53 publications

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Failed retrograde transport of NGF in a mouse model of Down's syndrome: Reversal of cholinergic neurodegenerative phenotypes following NGF infusion

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

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