Reduction in neurons immunoreactive for calcium-binding proteins in the anteroventral thalamic nuclei of individuals with Down syndrome

Topic: Brain proteins, microglia and lab models

The anterior thalamic nuclei are important for cognition, and memory in particular. However, little is known about how the anterior thalamic nuclei are affected in many neurological disorders partly due to difficulties in selective segmentation in in vivo scans, due to their size and location. Post-mortem studies, therefore, remain a valuable source of information about the status of the anterior thalamic nuclei. We used post-mortem tissue to assess the status of the anteroventral thalamic nucleus in Down syndrome using samples from males and females ranging from 22-65 years in age and comparing to tissue from age matched controls. As expected, there was increased beta-amyloid plaque expression in the Down syndrome group. While there was a significant increase in neuronal density in the Down syndrome group, the values showed more variation consistent with a heterogeneous population. The surface area of the anteroventral thalamic nucleus was smaller in the Down syndrome group suggesting the increased neuronal density was due to greater neuronal packing but likely fewer overall neurons. There was a marked reduction in the proportion of neurons immunoreactive for the calcium-binding proteins calbindin, calretinin, and parvalbumin in individuals with Down syndrome. These findings highlight the vulnerability of calcium-binding proteins in the anteroventral nucleus in Down syndrome, which could both be driven by, and exacerbate, Alzheimer-related pathology in this region.

Key findings

• While there was a significant increase in neuronal density in the Down syndrome group, the values showed more variation consistent with a heterogeneous population.
• The surface area of the anteroventral thalamic nucleus was smaller in the Down syndrome group suggesting the increased neuronal density was due to greater neuronal packing but likely fewer overall neurons.
• These findings highlight the vulnerability of calcium-binding proteins in the anteroventral nucleus in Down syndrome, which could both be driven by, and exacerbate, Alzheimer-related pathology in this region.

Why it matters

In post-mortem tissue, the anteroventral thalamic nucleus was smaller in people with Down syndrome and had a marked reduction in neurons immunoreactive for calcium-binding proteins. This descriptive brain tissue study does not test any treatment, cure or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.neuroscience.2024.08.004
• PubMed: 39127343
• Original source →
• Free full text: Neuroscience →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{perry2024-39127343,
  author  = {Perry, J. C. and Vann, S. D.},
  title   = {{Reduction in neurons immunoreactive for calcium-binding proteins in the anteroventral thalamic nuclei of individuals with Down syndrome}},
  journal = {Neuroscience},
  year    = {2024},
  doi     = {10.1016/j.neuroscience.2024.08.004},
  pmid    = {39127343},
  url     = {https://doi.org/10.1016/j.neuroscience.2024.08.004}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model Cell death and differentiation · 2014-05-23 · usefulness score 47/100 · Risk genes beyond APOE
• Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology Current Alzheimer research · 2016-01-01 · usefulness score 47/100 · Inflammation and the immune system
• Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome Journal of neuropathology and experimental neurology · 2003-09-01 · usefulness score 43/100 · Down syndrome and Alzheimer's

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Also tagged “down”

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