Back

Multifaceted impact of specialized neuropeptide-intensive neurons on the selective vulnerability in Alzheimer's disease

Li, M.; Larsen, P. A.

2023-11-16 neuroscience
10.1101/2023.11.13.566905 bioRxiv
Show abstract

INTRODUCTIONWidespread disruption of neuropeptide (NP) networks in Alzheimers disease (AD) and disproportionate absence of neurons expressing high NP-producing, coined as HNP neurons, have been reported for the entorhinal cortex (EC) of AD brains. Hypothesizing that functional features of HNP neurons are involved in the early pathogenesis of AD, we aim to understand the molecular mechanisms underlying these observations. METHODSMultiscale and spatiotemporal transcriptomic analysis was used to investigate AD-afflicted and healthy brains. Our focus encompassed NP expression dynamics in AD, AD-associated NPs (ADNPs) trajectories with aging, and the neuroanatomical distribution of HNP neuron. RESULTSFindings include that 1) HNP neurons exhibited heightened metabolic needs and an upregulation of gene expressions linked to protein misfolding; 2) dysfunctions of ADNP production occurred in aging and mild cognitive decline; 3) HNP neurons co-expressing ADNPs were preferentially distributed in brain regions susceptible to AD. DISCUSSIONWe identified potential mechanisms that contribute to the selective vulnerability of HNP neurons to AD. Our results indicate that the functions of HNP neurons predispose them to oxidative stress and protein misfolding, potentially serving as inception sites for misfolded proteins in AD.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

1
Alzheimer's & Dementia
177 papers in training set
Top 0.4%
14.0%
2
Molecular Neurodegeneration
○ 55 papers in training set
Top 0.1%
9.1%
Similar papers in this journal
3
Alzheimer's Research & Therapy
○ 57 papers in training set
Top 0.2%
6.4%
Similar papers in this journal
4
Acta Neuropathologica Communications
○ 89 papers in training set
Top 0.4%
5.3%
Similar papers in this journal
5
Molecular Psychiatry
○ 282 papers in training set
Top 1%
5.0%
Similar papers in this journal
6
Neurobiology of Disease
○ 148 papers in training set
Top 0.9%
4.1%
7
Acta Neuropathologica
○ 58 papers in training set
Top 0.4%
3.5%
8
Scientific Reports
○ 3612 papers in training set
Top 40%
2.5%
9
Journal of Alzheimer’s Disease
○ 50 papers in training set
Top 0.5%
2.4%
50% of probability mass above
10
eBioMedicine
○ 183 papers in training set
Top 2%
2.4%
11
Nature Communications
○ 5641 papers in training set
Top 39%
2.4%
12
Translational Neurodegeneration
○ 10 papers in training set
Top 0.1%
1.9%
13
Neuropathology and Applied Neurobiology
○ 15 papers in training set
Top 0.2%
1.8%
14
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
○ 42 papers in training set
Top 0.7%
1.5%
15
Nature Aging
○ 60 papers in training set
Top 1%
1.5%
16
ACS Chemical Neuroscience
● 67 papers in training set
Top 0.8%
1.5%
17
iScience
○ 1154 papers in training set
Top 23%
1.4%
18
Annals of Neurology
○ 64 papers in training set
Top 1%
1.4%
19
Neurobiology of Aging
○ 107 papers in training set
Top 1%
1.2%
20
eLife
● 5828 papers in training set
Top 58%
1.2%
21
Cells
○ 249 papers in training set
Top 4%
1.2%
22
Aging Cell
○ 165 papers in training set
Top 2%
1.2%
23
Brain
◐ 168 papers in training set
Top 2%
1.2%
24
Journal of Neuroinflammation
○ 61 papers in training set
Top 0.9%
1.2%
25
Cell Reports
○ 1498 papers in training set
Top 24%
1.1%
26
Translational Psychiatry
○ 260 papers in training set
Top 3%
1.1%
27
GeroScience
○ 109 papers in training set
Top 2%
1.1%
28
Frontiers in Aging Neuroscience
○ 74 papers in training set
Top 1%
1.0%
29
Brain Communications
◐ 166 papers in training set
Top 3%
1.0%
30
Communications Medicine
○ 113 papers in training set
Top 4%
0.9%