We present the case of a 49-year-old male diagnosed with trisomy 21 at an early age, who developed severe intellectual deficiency and progressive muscle weakness of the upper limbs at the age of 47.
He also complained of pain in the shoulders, and became unable to move his right arm within months. The symptoms worsened over the following year. He progressively stopped walking, developed dysphagia, further impairment of the lower limbs and eventually died.
At the autopsy, the patient presented characteristic craniofacial morphological features of Down syndrome. Macroscopic examination of the brain showed atrophy of the superior temporal gyrus and the frontoparietal cortex, a small hippocampus and dilatation of the lateral ventricles.
Microscopic examination of the brain showed typical features of Alzheimer’s disease with amyloid deposits in the cerebral cortex, basal ganglia and cerebellar cortex. Gallyas staining showed the presence of numerous neuritic plaques and widespread neurofibrillary degeneration at the level of the hippocampus. Immunohistological stains for alpha synuclein did not reveal the presence of Lewy bodies.
The spinal cord examination showed atrophy of the corticospinal tract. CD68 immunohistochemistry revealed abundant macrophages in the medullary pyramids and lateral columns and an associated microglial reaction. TDP-43 immunohistochemistry showed a filamentous staining in the cytoplasm and a loss of nuclear staining within motor-neurons. Ubiquitin immunohistochemistry showed weak staining of some spinal nerve roots.
A connection between Alzheimer’s disease and Down syndrome has been described extensively in the literature. The higher risk for Alzheimer's disease in people with Down syndrome has been attributed to increased production of amyloid beta due to an extra copy of chromosome 21, but other genes on chromosome 21 may also play a role, such as superoxide dismutase (SOD1). Little is known about the consequences of trisomy 21 for other neurodegenerative diseases. The present case shows that neurodegenerative disease in Down syndrome patients can take other forms besides Alzheimer’s disease, including amyotrophic lateral sclerosis.
Conflictsof Interest:
None.
