Comparison between Alzheimer’s disease (AD) in Down syndrome (DS) vs. sporadic AD (sAD)
| Feature | AD in DS | sAD |
|---|---|---|
| Age of onset | Early onset (commonly 40–50 years) | Late onset (typically > 65 years) |
| Genetic factors | Trisomy 21→Overexpression of APP gene (chromosome 21) | APOEε4 allele is a major risk factor; no APP gene overexpression |
| Amyloid-β deposition | Begins in teens–twenties; nearly universal by age 40 | Later onset; variable presence |
| Neurofibrillary tangles (tau pathology) | Develop later than amyloid but at younger ages than in sAD | Correlates with disease severity; gradual accumulation |
| Brain atrophy pattern | Early hippocampal and cortical atrophy; cerebellar involvement may be less pronounced | Prominent hippocampal, temporal, and parietal lobe atrophy |
| Cognitive profile | Baseline intellectual disability complicates diagnosis; early signs: behavior/personality changes, decline in adaptive skills | Prominent memory loss; later language, visuospatial, and executive deficits |
| Neuroimaging (MRI/PET) | Early amyloid PET positivity; structural MRI shows earlier atrophy | Amyloid PET positivity later; progressive cortical atrophy |
| Cholinergic system involvement | Significant degeneration of basal forebrain cholinergic neurons | Similar degeneration observed |
| Seizure prevalence | Higher incidence of seizures (up to 50% late in disease) | Lower seizure incidence (~10–22%) |
| Rate of progression | May be faster after onset | Variable, but generally more gradual |
| Neurological comorbidities | Congenital brain differences, hypothyroidism, epilepsy | Vascular risk factors (hypertension, diabetes, etc.) are more common |
| Diagnosis challenges | Harder to detect due to pre-existing cognitive impairment | Easier to detect due to prior cognitive baseline |
| Neuropathological hallmarks | Classic AD pathology is universally present by age 40 | Pathology variable and age-dependent |
APP: amyloid precursor protein; APOEε4: apolipoprotein E epsilon4; MRI: magnetic resonance imaging; PET: positron emission tomography
OG: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. EDdlC, IGLM, JAGC, and JAVP: Investigation, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
Not applicable.
Not applicable.
Not applicable.
Not applicable.
This work was supported by PAPIME [PE302323] (OG). IGLM and JAGC received a CONAHCYT scholarship for master’s studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2025.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.