Journal article
Norepinephrine-mediated regulation of endogenous Aβ 42 peptide levels: effects of noradrenergic depletion and restoration
MedScience, Forthcoming
24 Jul 2026
PMID: 42493706
Abstract
The locus coeruleus (LC), a cluster of noradrenergic neurons in the dorsal pons, is the brain's main source of norepinephrine (NE), crucial for memory, cognition, and stress response. NE dysregulation has been linked to mood disorders, chronic stress, and neurodegenerative diseases such as Alzheimer's disease (AD). Amyloid-β
(Aβ
) is a key protein in AD pathology, and forms plaques that trigger neurodegeneration. Studies show elevated Aβ
levels are associated with anxiety symptoms, even in cognitively normal individuals. Previous research suggests a positive correlation between NE and Aβ
, with Aβ
present in NE-producing LC neurons. NE may affect Aβ
levels through adrenergic receptors on neurons or microglia. However, the exact role of NE in modulating Aβ
remains unclear. Using the NE depletion models, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) lesions and dopamine β-hydroxylase (DBH) knockout (KO) mice, researchers found reduced Aβ
levels without changes in amyloid precursor protein processing. A newer model, DBH internal ribosome entry site-Cre × floxed tyrosine hydroxylase (DBH-IRES-Cre × floxed-TH) preserved dopamine (DA) but eliminated NE in adrenergic neurons, further supporting the specific influence of NE on Aβ
. Findings indicate that decreased Aβ
in NE-depleted mice stems not from altered DA but from NE loss. This highlights the NE-mediated regulation of endogenous Aβ
and the role of NE in AD-related pathology.
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Details
- Title
- Norepinephrine-mediated regulation of endogenous Aβ 42 peptide levels: effects of noradrenergic depletion and restoration
- Creators
- Isaiah Hoffman (Corresponding Author) - Charles R. Drew University of Medicine and ScienceJennifer A Ross - Drexel UniversityMarissa Tumasz - Philadelphia College of Osteopathic MedicineSteven A Thomas - University of PennsylvaniaElisabeth J Van Bockstaele - Drexel University
- Publication Details
- MedScience, Forthcoming
- Publisher
- Springer Nature
- Number of pages
- 7
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Graduate School - Dean's Office; Pharmacology and Physiology
- Web of Science ID
- WOS:001828535800001
- Other Identifier
- 991022197297704721