Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis

Lyness, Scott A.; Zarow, Chris; Chui, Helena C.

doi:10.1016/s0197-4580(02)00057-x

Cited by 213 publications

(140 citation statements)

References 139 publications

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“…Thus, although intrinsic vulnerability of MAergic neurons could be a factor, it is clear that additional factors that are specific for the APPswe/PS1⌬E9 mouse model determine the pattern of MAergic neurodegeneration. Again, this view is consistent with the observed pattern of MAergic neurodegeneration in AD cases (Marcyniuk et al, 1986;Mann et al, 1987;German et al, 1992;Parvizi et al, 2001;Lyness et al, 2003).…”

Section: Discussionsupporting

confidence: 90%

“…In addition to the degeneration of cortical and hippocampal neurons, AD is associated with the early and progressive degeneration of monoaminergic (MAergic) neurons [serotonergic (5-HT) neurons in the raphe and the noradrenergic (NA) neurons in the locus ceruleus (LC)] (Marcyniuk et al, 1986;Zweig et al, 1988;German et al, 1992;Rub et al, 2000;Parvizi et al, 2001;Lyness et al, 2003;Grudzien et al, 2007). Analysis of MAergic neuropathology in AD cases indicate that neurons that project to cortex (anterior raphe/LC) are pathologically affected, whereas neurons without cortical projections (posterior raphe/LC) are free of pathological changes (Marcyniuk et al, 1986;German et al, 1992;Parvizi et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

Liu¹,

Yoo²,

Savonenko³

et al. 2008

J. Neurosci.

180

179

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␤-Amyloid (A␤) pathology is an essential pathogenic component in Alzheimer's disease (AD). However, the significance of A␤ pathology, including A␤ deposits/oligomers and glial reactions, to neurodegeneration is unclear. In particular, despite the A␤ neurotoxicity indicated by in vitro studies, mouse models with significant A␤ deposition lack robust and progressive loss of forebrain neurons. Such results have fueled the view that A␤ pathology is insufficient for neurodegeneration in vivo. In this study, because monoaminergic (MAergic) neurons show degenerative changes at early stages of AD, we examined whether the APPswe/PS1⌬E9 mouse model recapitulates progressive MAergic neurodegeneration occurring in AD cases. We show that the progression forebrain A␤ deposition in the APPswe/ PS1⌬E9 model is associated with progressive losses of the forebrain MAergic afferents. Significantly, axonal degeneration is associated with significant atrophy of cell bodies and eventually leads to robust loss (ϳ50%) of subcortical MAergic neurons. Degeneration of these neurons occurs without obvious local A␤ or tau pathology at the subcortical sites and precedes the onset of anxiety-associated behavior in the mice. Our results show that a transgenic mouse model of A␤ pathology develops progressive MAergic neurodegeneration occurring in AD cases.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

Liu¹,

Yoo²,

Savonenko³

et al. 2008

J. Neurosci.

180

179

View full text Add to dashboard Cite

show abstract

“…In addition to the degeneration of cortical and hippocampal neurons, Alzheimer disease is associated with the early and progressive degeneration of monoaminer gic neurons. 15,16 For these reasons, the development of hybrid drugs that behave as dual inhibitors of both ChEs and MAO are being actively produced to treat Alzheimer disease symp toms and potentially slow the disease progression. [17][18][19] In this regard, we have conceived a compound coded ASS234 (see the structure in the Methods section), [20][21][22] that is a a multi potent AChE/MAO inhibitor with the ability to cross the blood-brain barrier and that shows antioxidant and neuro protective properties with inhibitory effects on Aβ aggrega tion.…”

Section: J Psychiatry Neurosci 2017;42(1)mentioning

confidence: 99%

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

Serrano

Herrero-Labrador

Futch

et al. 2017

JPN

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“…In a meta-analysis of this research, neuronal density in the locus ceruleus, dorsal raphe nucleus, and substantia nigra was reduced in AD. 20 However, there has been little research on the relation of locus ceruleus noradrenergic neuronal density to cognitive functioning. Among persons with dementia, having few locus ceruleus neurons has been associated with lower level of cognition in some studies 21,22 but not others.…”

Section: Figurementioning

confidence: 99%

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline

et al. 2013

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Objective: To test the hypothesis that higher neuronal density in brainstem aminergic nuclei contributes to neural reserve.Methods: Participants are 165 individuals from the Rush Memory and Aging Project, a longitudinal clinical-pathologic cohort study. They completed a mean of 5.8 years of annual evaluations that included a battery of 19 cognitive tests from which a previously established composite measure of global cognition was derived. Upon death, they had a brain autopsy and uniform neuropathologic examination that provided estimates of the density of aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area plus summary measures of neuronal neurofibrillary tangles and Lewy bodies from these nuclei and medial temporal lobe and neocortex.Results: Neuronal densities in each nucleus were approximately normally distributed. In separate analyses, higher neuronal density in each nucleus except the ventral tegmental area was associated with slower rate of cognitive decline, but when modeled together only locus ceruleus neuronal density was related to cognitive decline (estimate 5 0.003, SE 5 0.001, p , 0.001). Higher densities of tangles and Lewy bodies in these brainstem nuclei were associated with faster cognitive decline even after controlling for pathologic burden elsewhere in the brain. Locus ceruleus neuronal density, brainstem tangles, and brainstem Lewy bodies had independent associations with rate of cognitive decline. In addition, at higher levels of locus ceruleus neuronal density, the association of Lewy bodies with cognitive decline was diminished. ) or their components (synapses 8,9 ) in key locations. This approach allows collection of neuronal and pathologic data from the same brain regions, facilitating examination of their conjoint correlations with cognition. ConclusionThe present study examines the associations among neuronal density, neurodegenerative lesions, and change in cognitive function. We assessed neuronal density in brainstem aminergic nuclei (i.e., locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area) because these nuclei support multiple cognitive processes, synthesize important monoamines that function as neurotransmitters and neuromodulators, are therapeutic targets for cognitive enhancement, 10 and bear a disproportionate burden of age-related neurodegeneration. 11,12 Participants from the Rush Memory and Aging Project had annual cognitive testing for a mean of 5.8 years, died, and underwent a neuropathologic examination that yielded neuronal counts for each brainstem nucleus From the Rush Alzheimer's Disease

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Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis

Cited by 213 publications

References 139 publications

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline

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