Scientific article
English

Dopaminergic deficits along the spectrum of Alzheimer’s disease

Published inMolecular psychiatry, vol. 30, no. 7, p. 3069-3076
Publication date2025-07
First online date2025-01-31
Abstract

Both post-mortem and in vivo data argue for dopamine dysfunction in patients with Alzheimer's Disease (AD). However, the timing and regional progression of dopaminergic systems alterations in AD are still debated. The aim of the study was to investigate in vivo the pattern of dopaminergic changes and connectivity using DAT-SPECT imaging in patients across the AD spectrum. Fifty-nine AD patients (n = 21 AD-MCI; n = 38 AD-DEM) and a control group (CG) of n = 45 age- and sex-matched individuals entered the study and underwent 123I-FP-CIT dopaminergic imaging. The occipital binding was used as reference region to obtain single-subject binding in different brain regions. Between-group differences in 123I-FP-CIT binding in both mesolimbic and nigrostriatal dopaminergic pathways were assessed using an ANCOVA test, adjusting for the effect of center of imaging acquisition, age, and sex. Regions resulting from the voxel-wise direct comparison between AD-MCI and AD-DEM were considered as a seed of interest for a voxel-wise interregional correlation analysis. Both AD-MCI and AD-DEM patients showed dopaminergic depletion within the basal ganglia, whereas cortico-limbic regions (namely hippocampus, amygdala, anterior and middle cingulate, frontal cortex and thalamus) resulted impaired only in the dementia phase. The brain voxel-wise interregional correlation analysis showed a progressive pattern of disruption of caudate/thalamus dopaminergic connectivity to hippocampus and amygdala from AD-MCI to AD-DEM stages. This study indicates basal ganglia dopaminergic alterations and connectivity disruption in the nigrostriatal and mesolimbic systems already in early stage AD, extending to several cortico-limbic regions in dementia phases.

Keywords
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Cognitive Dysfunction / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neural Pathways / metabolism
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tropanes
Funding
  • Ministero della Salute [RF-2018-12366209]
  • Ministero dell'Istruzione, dell'Università e della Ricerca [MNESYS project (DN.1553)]
Citation (ISO format)
PILOTTO, Andrea et al. Dopaminergic deficits along the spectrum of Alzheimer’s disease. In: Molecular psychiatry, 2025, vol. 30, n° 7, p. 3069–3076. doi: 10.1038/s41380-025-02913-5
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/s41380-025-02913-5
Journal ISSN1359-4184
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