Lower Plasma Serotonin is Associated with Higher Amyloid Burden, Hippocampal Atrophy, and Cognitive decline in Alzheimer’s Disease: A 24-Month Longitudinal Study

Alenina N, Klempin F (2015) The role of serotonin in adult hippocampal neurogenesis. Behav Brain Res 277:49–57. https://doi.org/10.1016/j.bbr.2014.07.038

Article  CAS  PubMed  Google Scholar 

Alzenaidi F, Aldoweesh O, Alghofaili S, Fadel A, Lasloom RAA, Alharbi D et al (2025) Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer’s disease and related dementias: a systematic review and meta-analysis of brain metabolic and adverse event data. Metab Open. https://doi.org/10.1016/j.metop.2025.100389

Article  Google Scholar 

Azargoonjahromi A (2024a) The duality of amyloid-β: its role in normal and Alzheimer’s disease states. Mol Brain 17(1):44. https://doi.org/10.1186/s13041-024-01118-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Azargoonjahromi A (2024b) Serotonin enhances neurogenesis biomarkers, hippocampal volumes, and cognitive functions in Alzheimer’s disease. Mol Brain 17(1):93. https://doi.org/10.1186/s13041-024-01169-4

Article  CAS  PubMed  PubMed Central  Google Scholar 

Azargoonjahromi A (2025) Plasma tryptophan levels are linked to hippocampal integrity and cognitive function in individuals with mild cognitive impairment. Brain Imaging Behav 19(2):485–496. https://doi.org/10.1007/s11682-025-00992-0

Article  PubMed  Google Scholar 

Azargoonjahromi A, Initiative ADN (2024) Serotonin enhances neurogenesis biomarkers, hippocampal volumes, and cognitive functions in Alzheimer’s disease. Mol Brain 17(1):93

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borue X, Chen J, Condron BG (2007) Developmental effects of ssris: lessons learned from animal studies. Int J Dev Neurosci 25(6):341–347. https://doi.org/10.1016/j.ijdevneu.2007.06.003

Article  CAS  PubMed  PubMed Central  Google Scholar 

Butzlaff M, Ponimaskin E (2016) The role of serotonin receptors in Alzheimer’s disease. Oper Med Physiol 1:91–100

Google Scholar 

Celada P, Puig MV, Artigas F (2013) Serotonin modulation of cortical neurons and networks. Front Integr Neurosci. https://doi.org/10.3389/fnint.2013.00025

Article  PubMed  PubMed Central  Google Scholar 

Chai A (2025) Pleiotropic neurotransmitters: neurotransmitter-receptor crosstalk regulates excitation-inhibition balance in social brain functions and pathologies. Front Neurosci. https://doi.org/10.3389/fnins.2025.1552145

Article  PubMed  PubMed Central  Google Scholar 

Chakraborty S, Lennon JC, Malkaram SA, Zeng Y, Fisher DW, Dong H (2019) Serotonergic system, cognition, and BPSD in Alzheimer’s disease. Neurosci Lett 704:36–44

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen K, Roontiva A, Thiyyagura P, Lee W, Liu X, Ayutyanont N et al (2015) Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region. J Nucl Med 56(4):560–6. https://doi.org/10.2967/jnumed.114.149732

Article  CAS  PubMed  Google Scholar 

Chen M, Wang C, Lin Y, Chen Y, Xie W, Huang X et al (2024) Dorsal raphe nucleus-hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice. Transl Neurodegener 13(1):34. https://doi.org/10.1186/s40035-024-00425-w

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chow TW, Pollock BG, Milgram NW (2007) Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer’s disease. Neuropsychiatr Dis Treat 3(5):627–636

CAS  PubMed  PubMed Central  Google Scholar 

Cirrito JR, Disabato BM, Restivo JL, Verges DK, Goebel WD, Sathyan A et al (2011) Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans. Proc Natl Acad Sci U S A 108(36):14968–73. https://doi.org/10.1073/pnas.1107411108

Article  PubMed  PubMed Central  Google Scholar 

Cirrito JR, Wallace CE, Yan P, Davis TA, Gardiner WD, Doherty BM et al (2020) Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model. Neurology 95(19):e2666–e74. https://doi.org/10.1212/wnl.0000000000010733

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cochet M, Donneger R, Cassier E, Gaven F, Lichtenthaler SF, Marin P et al (2013) 5-HT4 receptors constitutively promote the non-amyloidogenic pathway of APP cleavage and interact with ADAM10. ACS Chem Neurosci 4(1):130–40. https://doi.org/10.1021/cn300095t

Article  CAS  PubMed  Google Scholar 

Dale E, Pehrson AL, Jeyarajah T, Li Y, Leiser SC, Smagin G et al (2016) Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr 21(2):143–61. https://doi.org/10.1017/s1092852915000425

Article  PubMed  Google Scholar 

Dauphinot V, Calvi S, Moutet C, Xie J, Dautricourt S, Batsavanis A et al (2024) Reliability of the assessment of the clinical dementia rating scale from the analysis of medical records in comparison with the reference method. Alzheimers Res Ther 16(1):198. https://doi.org/10.1186/s13195-024-01567-9

Article  PubMed  PubMed Central  Google Scholar 

Dolgacheva LP, Zinchenko VP, Nadeev AD, Goncharov NV (2025) Serotonergic regulation in Alzheimer’s disease. Int J Mol Sci. https://doi.org/10.3390/ijms26115218

Article  PubMed  PubMed Central  Google Scholar 

Dolgacheva LP, Zinchenko VP, Nadeev AD, Goncharov NV (2025) Serotonergic regulation in Alzheimer’s disease. Int J Mol Sci 26(11):5218

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ehrenberg AJ, Nguy AK, Theofilas P, Dunlop S, Suemoto CK, Di Lorenzo Alho AT et al (2017) Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer’s disease. Neuropathol Appl Neurobiol 43(5):393–408. https://doi.org/10.1111/nan.12387

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fernandes BS, Inam ME, Enduru N, Quevedo J, Zhao Z (2023) The kynurenine pathway in Alzheimer’s disease: a meta-analysis of central and peripheral levels. Braz J Psychiatry 45(3):286–297

PubMed  Google Scholar 

Giannoni P, Gaven F, De Bundel D, Baranger K, Marchetti-Gauthier E, Roman FS et al (2013) Early administration of RS 67333, a specific 5-HT4 receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of alzheimer’s disease. Front Aging Neurosci 5–2013. https://doi.org/10.3389/fnagi.2013.00096

Hochstrasser T, Hohsfield LA, Sperner-Unterweger B, Humpel C (2013) β‐amyloid induced effects on cholinergic, serotonergic, and dopaminergic neurons is differentially counteracted by anti‐inflammatory drugs. J Neurosci Res 91(1):83–94

Article  CAS  PubMed  Google Scholar 

Hsu T-W, Stubbs B, Liang C-S, Chen T-Y, Yeh T-C, Pan C-C et al (2021) Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: a systematic review and meta-analysis. Ageing Res Rev 69:101362

Article  CAS  PubMed  Google Scholar 

Khan NS, Uribe Isaza J, Rouhi N, Jamani NF, Jabeen S, Gill AK et al (2024) Behavioral and neurophysiological implications of pathological human tau expression in serotonin neurons. ACS Chem Neurosci 15(5):932–43. https://doi.org/10.1021/acschemneuro.3c00626

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kumar AM, Sevush S, Kumar M, Ruiz J, Eisdorfer C (1995) Peripheral serotonin in Alzheimer’s disease. Neuropsychobiology 32(1):9–12. https://doi.org/10.1159/000119205

Article  CAS  PubMed  Google Scholar 

Leschik J, Gentile A, Cicek C, Péron S, Tevosian M, Beer A et al (2022) Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis. Prog Neurobiol 217:102333. https://doi.org/10.1016/j.pneurobio.2022.102333

Article  CAS  PubMed 

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