Somatostatin interneurons and the pathogenesis of Alzheimer's disease
Victor N.Almeida1
Guilherme S.V.Higa2
1.Laboratório de Neurociências(LIM 27),Institute of Psychiatry(IPq),Faculty of Medicine,University of São Paulo(USP),São Paulo,Brazil2.Laboratory of Neurophysiology,Department of Biophysics and Physiology,Institute of Biomedicine(ICB),University of São Paulo,São Paulo,Brazil;Department of Biochemistry,Institute of Chemistry,University of São Paulo,São Paulo,Brazil
摘要：It was in the 1980s that research on somatostatin(SST) in Alzheimer's disease (AD) truly gained traction,demonstrating consistent colocalization with amyloid-β (Aβ),along with massive SST/SST cell losses(Almeida,2024). Although the field already had some grasp over the neuroendocrine and hypothalamic functions of the peptide,very little was known about the GABAergic interneurons (SST-INs) that synthesize it in cortical/hippocampal regions. Quite excitingly,over 40 years later,research has grown effervescent.Namely,SST-INs show great promise as therapeutic targets for medical intervention in AD and potential players in its aetiopathogenesis. Our perspective aims to provide an update on a molecular model,authored by one of us,which places SST-INs at the fulcrum of AD's aetiopathogenesis (Almeida,2024). In light of spatial constraints,we will lay emphasis specifically on how the SST model is capable of satisfying Occam's razor by placing SST-IN hyperactivity at "stage 0" for neurodegeneration/proteinopathy,and how it sheds light on the paradoxical polarization of p-tau to the hippocampus versus Aβ to the cortex.
机标关键词：alzheimerdiseaseinterneuronspathogenesissomatostatin
论文发表日期：2026-03-30
在线出版日期：2026-03-18（本平台首次上网日期，不代表文献的发表时间）
页数：2( 1128-1129 )