A Narrative Review of the Genetic Factors Involved in the Development of Alzheimer’s Disease in Patients with Down Syndrome
Cecilia Villegas Robles1, Carolina Villegas Robles2, Ana Paula Arizpe Revilla1, Mauricio Andrés Salinas Santander1, Victor de Jesús Suárez Valencia1
1Autonomous University of Coahuila, 2University of Monterrey
Objective:

To systematically examine the existing literature on the genetic factors involved in the development of Alzheimer’s disease in individuals with Down syndrome, and to analyze data regarding its prevalence, clinical manifestations, diagnostic modalities, and therapeutic strategies.

Background:

Down syndrome is the most common chromosomal disorder; it is associated with an accelerated aging process, which increases the risk of developing Alzheimer’s disease at an early age compared to the general population. The genetic disturbance in patients with Down syndrome has shown that several genetic factors contribute to the pathogenesis of Alzheimer’s disease.

Design/Methods:

A comprehensive search was conducted in the PubMed, SciELO, Scopus, and Google Scholar databases in August 2025. Articles published between 2020 and 2025 that met the predefined inclusion criteria were selected. A total of sixty-four studies were included, all of which were reviewed in full, and a narrative synthesis of the findings was subsequently performed.

Results:

The prevalence of Alzheimer’s disease was shown to be above 60% in Down syndrome patients over 65 years, the mean age at diagnosis was 53 years, and the mortality occurred around 59 years. The main genetic factor identified was the overexpression of the APP gene, along with other genes such as DYRK1A, RCAN1, SOD1, APOEε4, SYNJ1 and genes involved in the immune response. Additional factors - including obstructive sleep apnea, vascular pathologies, thyroid disfunction and cerebral insulin resistance - contribute to the progression of the disease. Diagnosis remains a challenge due to the pre-existent intellectual disability and the atypical clinical presentation; however, the development of adapted neuropsychological test, biomarkers, and neuroimaging techniques are expected to facilitate early diagnosis.

Conclusions:

The association between both diseases arises from complex genetic factors that promote an early onset and accelerated progression. Timely diagnosis and intervention play a key role in improving the well-being of patients and those close to them.

10.1212/WNL.0000000000215824
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