Evidence map›Paper›PMID 36475335›Full record

ArticleCurrent neuropharmacology2023

Sex, Age, and Regional Differences in

Cristina Sanfilippo, Loretta Giuliano, Paola Castrogiovanni, Rosa Imbesi, Martina Ulivieri, Francesco Fazio, Kaj Blennow, Henrik Zetterberg, Michelino Di Rosa

Open access · greenAbstract read
In one paragraph

Article in Current neuropharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Reconstructing cerebral lymphatic clearance: an emerging target in the Alzheimer's disease therapeutic pipeline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 4 countries.

Cristina SanfilippoDepartment G.F. Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy.
Loretta GiulianoDepartment G.F. Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy.
Paola CastrogiovanniDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy.
Rosa ImbesiDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy.
Martina UlivieriDepartment of Psychiatry, Health Science, University of California San Diego, San Diego La Jolla, CA, USA.
Francesco FazioDepartment of Psychiatry, Health Science, University of California San Diego, San Diego La Jolla, CA, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Michelino Di RosaDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy.
University of Catania · ITUniversity of California, San Diego · USUniversity of Gothenburg · SE

Funding

European Research Council 681712
6 · The paper itself

Abstract

backgroundCholinergic hypofunction and sleep disturbance are hallmarks of Alzheimer's disease (AD), a progressive disorder leading to neuronal deterioration. Muscarinic acetylcholine receptors (M1-5 or mAChRs), expressed in hippocampus and cerebral cortex, play a pivotal role in the aberrant alterations of cognitive processing, memory, and learning, observed in AD. Recent evidence shows that two mAChRs, M1 and M3, encoded by CHRM1 and CHRM3 genes, respectively, are involved in sleep functions and, peculiarly, in rapid eye movement (REM) sleep.

methodsWe used twenty microarray datasets extrapolated from post-mortem brain tissue of nondemented healthy controls (NDHC) and AD patients to examine the expression profile of CHRM1 and CHRM3 genes. Samples were from eight brain regions and stratified according to age and sex.

resultsCHRM1 and CHRM3 expression levels were significantly reduced in AD compared with ageand sex-matched NDHC brains. A negative correlation with age emerged for both CHRM1 and CHRM3 in NDHC but not in AD brains. Notably, a marked positive correlation was also revealed between the neurogranin (NRGN) and both CHRM1 and CHRM3 genes. These associations were modulated by sex. Accordingly, in the temporal and occipital regions of NDHC subjects, males expressed higher levels of CHRM1 and CHRM3, respectively, than females. In AD patients, males expressed higher levels of CHRM1 and CHRM3 in the temporal and frontal regions, respectively, than females.

conclusionThus, substantial differences, all strictly linked to the brain region analyzed, age, and sex, exist in CHRM1 and CHRM3 brain levels both in NDHC subjects and in AD patients.

Indexed as

Alzheimer DiseaseBiopsyBrainFemaleHumansMaleReceptor, Muscarinic M1Receptor, Muscarinic M3SleepCHRM1 protein, humanCHRM3 protein, humanReceptor, Muscarinic M1Receptor, Muscarinic M3Alzheimer’s diseasebioinformaticsCHRM1CHRM3REM-Sleepsleep disturbance

Identifiers

PMID36475335
PMCPMC10207911
OpenAlexW4311845880

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.