¶ Down Syndrome and Alzheimer's Disease
¶ Introduction
Down Syndrome and Alzheimer's Disease represents affecting millions worldwide. This page provides comprehensive information about the disease, including its mechanisms, symptoms, diagnosis, and treatment approaches.
¶ Overview
Down syndrome (DS), caused by trisomy of chromosome 21, represents the most common genetic cause of intellectual disability and is now recognized as the most prevalent genetically determined form of [Alzheimer's disease[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers--TEMP--/diseases)--FIX-- (AD). Virtually all individuals with DS develop the neuropathological hallmarks of AD—[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- ([Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- plaques and tau] neurofibrillary tangles—by age 40, and clinical dementia affects approximately 70–80% of individuals by age 60–70 1(https://pubmed.ncbi.nlm.nih.gov/34687637/). The critical genetic link is the triplication of the [amyloid precursor protein[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- gene located on chromosome 21, resulting in lifelong overproduction of [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- peptides 2(https://pubmed.ncbi.nlm.nih.gov/27983553/).
With improved medical care extending the life expectancy of individuals with DS from approximately 25 years in the 1980s to over 60 years today, [Alzheimer's disease[/diseases/[alzheimers[/diseases/[alzheimers[/diseases/[alzheimers--TEMP--/diseases)--FIX-- has become the leading cause of death in this population 3(https://pubmed.ncbi.nlm.nih.gov/32029743/). The study of DS-associated AD (DS-AD) provides unique insights into the amyloid cascade hypothesis and offers a natural model for understanding the earliest stages of AD pathogenesis, years before symptom onset. The DS-AD population is increasingly recognized as critical for clinical trial design, given the predictable trajectory and genetic homogeneity of disease.
¶ Genetic Basis
¶ APP Gene Triplication
The central genetic driver of AD in DS is the presence of three copies of the [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- gene on chromosome 21. [This dosage imbalance leads to approximately 1.5-fold overexpression of [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- protein], resulting in chronically elevated production of [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- peptides, particularly the aggregation-prone [Aβ42] isoform 4(https://pubmed.ncbi.nlm.nih.gov/26651341/). Evidence supporting the central role of [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- triplication comes from rare cases of partial trisomy 21 that exclude the [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- locus, in which individuals do not develop AD neuropathology despite having DS-associated intellectual disability 2(https://pubmed.ncbi.nlm.nih.gov/27983553/).
The processing of [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- by [beta-secretase[/[gamma-secretase[/[gamma-secretase[/[gamma-secretase[/[gamma-secretase[/[gamma-secretase[/gamma-secretase follows the same amyloidogenic pathway as in sporadic and autosomal dominant AD, but the increased substrate availability from the third [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- copy accelerates [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- production throughout the lifespan. Notably, [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- accumulation in DS begins in utero, with detectable Aβ42 in fetal DS brain tissue, making DS the earliest-onset form of [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- pathology known link.
¶ Additional Chromosome 21 Genes
Beyond [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX--, chromosome 21 harbors several other genes that modulate AD risk and pathogenesis in DS:
- DYRK1A (Dual-specificity tyrosine-phosphorylation regulated kinase 1A): Overexpressed in DS, DYRK1A phosphorylates tau] protein] at multiple AD-relevant epitopes (Thr212, Ser202/Thr205) and promotes [neurofibrillary tangle] formation. It also phosphorylates [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- at Thr668, enhancing amyloidogenic processing 6(https://pubmed.ncbi.nlm.nih.gov/28807816/).
- RCAN1 (Regulator of Calcineurin 1): Overexpression inhibits calcineurin signaling, contributing to tau hyperphosphorylation], [oxidative stress[/mechanisms/[oxidative-stress[/mechanisms/[oxidative-stress[/mechanisms/[oxidative-stress--TEMP--/mechanisms)--FIX--, and mitochondrial dysfunction 7(https://pubmed.ncbi.nlm.nih.gov/32775597/).
- SOD1 (Superoxide Dismutase 1): Triplication leads to imbalanced antioxidant defense, paradoxically increasing oxidative stress via excess hydrogen peroxide production without commensurate increases in catalase activity 8(.
- ETS2 and BACE2: ETS2 is a transcription factor linked to [apoptosis[/entities/[apoptosis[/entities/[apoptosis[/entities/[apoptosis--TEMP--/entities)--FIX--, while BACE2 may serve a protective role by preferentially cleaving [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- within the [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- domain, potentially competing with amyloidogenic processing 3(https://pubmed.ncbi.nlm.nih.gov/32029743/).
¶ mTOR Pathway Dysregulation
The [mTOR[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration--TEMP--/mechanisms)--FIX-- signaling pathway is constitutively hyperactivated in DS brains. Elevated [mTOR[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration--TEMP--/mechanisms)--FIX-- activity suppresses [autophagy[/entities/[autophagy[/entities/[autophagy[/entities/[autophagy--TEMP--/entities)--FIX--, impairing the clearance of aggregated proteins including [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- and phosphorylated tau. This autophagy-lysosomal dysfunction creates a feedforward loop: reduced clearance leads to increased accumulation of toxic protein aggregates, which further impairs cellular proteostasis 6(https://pubmed.ncbi.nlm.nih.gov/28807816/).
¶ Neuropathology
¶ Amyloid Pathology
[Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- deposition in DS follows a predictable temporal sequence:
- Prenatal to adolescence: Soluble [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- levels are elevated; diffuse plaques appear in some individuals as early as age 12–15
- 20s–30s: Diffuse [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- plaques become widespread, particularly in frontal and temporal cortices
- 30s–40s: Neuritic plaques with dense amyloid cores appear, accompanied by early [cerebral amyloid angiopathy[/diseases/[cerebral-amyloid-angiopathy[/diseases/[cerebral-amyloid-angiopathy[/diseases/[cerebral-amyloid-angiopathy--TEMP--/diseases)--FIX-- (CAA)
- >40 years: Full AD neuropathology with extensive plaques, meeting Braak amyloid stages equivalent to moderate-to-severe AD 4(https://pubmed.ncbi.nlm.nih.gov/26651341/)
[Cerebral amyloid angiopathy[/diseases/[cerebral-amyloid-angiopathy[/diseases/[cerebral-amyloid-angiopathy[/diseases/[cerebral-amyloid-angiopathy--TEMP--/diseases)--FIX-- (CAA) is particularly prevalent in DS-AD, affecting over 90% of individuals over age 50. The DS-associated CAA is predominantly composed of Aβ40 deposited in leptomeningeal and cortical vessels, and carries significant risk for intracerebral hemorrhage and microbleeds 9(.
¶ Tau Pathology
[Neurofibrillary tangle] formation in DS-AD follows the classic Braak staging pattern of sporadic AD, beginning in the entorhinal [cortex[/brain-regions/[cortex[/brain-regions/[cortex[/brain-regions/[cortex--TEMP--/brain-regions)--FIX-- and [hippocampus[/brain-regions/[hippocampus[/brain-regions/[hippocampus[/brain-regions/[hippocampus--TEMP--/brain-regions)--FIX-- (stages I–II), then spreading to limbic structures (stages III–IV) and eventually to neocortical regions (stages V–VI). However, tau pathology in DS lags approximately 10–15 years behind amyloid deposition, consistent with the [amyloid cascade hypothesis] 1(https://pubmed.ncbi.nlm.nih.gov/34687637/).
The [locus coeruleus[/brain-regions/[locus-coeruleus[/brain-regions/[locus-coeruleus[/brain-regions/[locus-coeruleus--TEMP--/brain-regions)--FIX-- shows early vulnerability in DS-AD, with tau pathology appearing in this region before widespread cortical involvement, mirroring findings in sporadic AD and suggesting shared mechanisms of [selective neuronal vulnerability[/mechanisms/[selective-neuronal-vulnerability[/mechanisms/[selective-neuronal-vulnerability[/mechanisms/[selective-neuronal-vulnerability--TEMP--/mechanisms)--FIX-- 10(https://pubmed.ncbi.nlm.nih.gov/37056479/).
¶ neuroinflammation and Oxidative Stress
DS brains exhibit chronic [neuroinflammation[/mechanisms/[neuroinflammation[/mechanisms/[neuroinflammation[/mechanisms/[neuroinflammation--TEMP--/mechanisms)--FIX-- from early life, with activated [microglia[/entities/[microglia[/entities/[microglia[/entities/[microglia--TEMP--/entities)--FIX--.)
Proteomic analyses of DS cerebrospinal fluid (CSF) have revealed distinct immune and extracellular matrix protein signatures that differ from both late-onset and autosomal dominant AD, suggesting that DS-AD involves unique pathogenic pathways beyond simply accelerated amyloid deposition 12(https://www.nature.com/articles/s41467-025-61054-z).
¶ Clinical Features
¶ Cognitive Decline and Dementia
Clinical diagnosis of dementia in DS presents unique challenges because of baseline intellectual disability. Key features include:
- Prodromal phase (typically 30s–40s): Subtle changes in adaptive behavior, apathy, executive dysfunction, and personality changes that may precede memory impairment
- Early dementia (typically 40s–50s): Progressive memory loss, disorientation, decline in activities of daily living, and language deterioration
- Late dementia: Global cognitive decline, seizures (affecting 50–75% of DS-AD patients), incontinence, dysphagia, and loss of ambulation 1(https://pubmed.ncbi.nlm.nih.gov/34687637/)
The mean age of clinical dementia onset in DS is approximately 50–55 years, though there is considerable individual variation. [APOE[/[https[/[https[/[https[/[https[/[https[/https
/pubmed.ncbi.nlm.nih.gov/32029743/).
¶ Seizures
Epilepsy has a bimodal distribution in DS, with early childhood seizures (often West syndrome or febrile seizures) and late-onset seizures strongly associated with AD progression. New-onset seizures after age 40 in DS are a strong predictor of dementia and are often an early manifestation of AD-related neurodegeneration 13(https://pubmed.ncbi.nlm.nih.gov/32920658/).
¶ Behavioral and Psychiatric Features
Depression, anxiety, and behavioral regression are common in DS-AD and may precede cognitive decline. These features often respond poorly to standard pharmacotherapy, complicating management. Sleep disturbances, including obstructive sleep apnea (highly prevalent in DS), may independently accelerate AD pathology through impaired [glymphatic clearance] 1(https://pubmed.ncbi.nlm.nih.gov/34687637/).
¶ Biomarkers
¶ Plasma Biomarkers
Recent advances in blood-based biomarkers have transformed the ability to detect and monitor AD in DS:
- Phosphorylated tau 217 : Plasma [p-tau217[/entities/[p-tau217[/entities/[p-tau217[/entities/[p-tau217--TEMP--/entities)--FIX-- shows excellent diagnostic accuracy for detecting [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- positivity and tau pathology in DS, with levels rising approximately 10 years before clinical dementia onset 14(https://pubmed.ncbi.nlm.nih.gov/34441934/)
- [Neurofilament light chain[/proteins/[nfl-protein[/proteins/[nfl-protein[/proteins/[nfl-protein--TEMP--/proteins)--FIX-- (NfL): Plasma [NfL[/entities/[neurofilament-light[/entities/[neurofilament-light[/entities/[neurofilament-light--TEMP--/entities)--FIX-- is elevated in DS-AD and correlates with neurodegeneration and cognitive decline; it is a strong predictor of conversion from asymptomatic to symptomatic AD
- [GFAP[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein--TEMP--/entities)--FIX--: Plasma [glial fibrillary acidic protein[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein--TEMP--/entities)--FIX-- reflects astrocytic activation and is elevated in DS-AD, potentially tracking neuroinflammation alongside neurodegeneration 15(https://pubmed.ncbi.nlm.nih.gov/40219863/)
A 2025 systematic review and meta-analysis confirmed that plasma [p-tau217[/entities/[p-tau217[/entities/[p-tau217[/entities/[p-tau217--TEMP--/entities)--FIX--, [NfL[/entities/[neurofilament-light[/entities/[neurofilament-light[/entities/[neurofilament-light--TEMP--/entities)--FIX--, and [GFAP[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein[/entities/[glial-fibrillary-acidic-protein--TEMP--/entities)--FIX-- are robust biomarkers for AD detection in DS, with [p-tau217[/entities/[p-tau217[/entities/[p-tau217[/entities/[p-tau217--TEMP--/entities)--FIX-- showing the highest diagnostic accuracy for [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX---positive status 15(https://pubmed.ncbi.nlm.nih.gov/40219863/).
¶ Neuroimaging Biomarkers
- [amyloid PET[/entities/[amyloid-pet[/entities/[amyloid-pet[/entities/[amyloid-pet--TEMP--/entities)--FIX--: Shows progressive [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- accumulation beginning in the striatum (earlier than in sporadic AD), followed by cortical spread. PET-positive scans are seen in most DS individuals by age 40
- [Tau[/entities/[tau-protein[/entities/[tau-protein[/entities/[tau-protein--TEMP--/entities)--FIX-- PET: Demonstrates neurofibrillary tangle distribution matching Braak staging
- Structural MRI: Reveals hippocampal atrophy, cortical thinning, and enlargement of perivascular spaces progressing with AD stage
- FDG-PET: Shows temporoparietal hypometabolism characteristic of AD 1(https://pubmed.ncbi.nlm.nih.gov/34687637/)
¶ Exosomal Biomarkers
Neuronal-derived exosomes from plasma of DS adults contain elevated levels of Aβ42, phosphorylated tau, and other AD-related proteins years before clinical symptoms, representing a promising non-invasive biomarker modality 5(https://pubmed.ncbi.nlm.nih.gov/28882786/).
¶ Therapeutic Approaches
¶ Anti-Amyloid Therapies
The approval of [lecanemab[/treatments/[lecanemab[/treatments/[lecanemab[/treatments/[lecanemab--TEMP--/treatments)--FIX-- and [donanemab[/treatments/[donanemab[/treatments/[donanemab[/treatments/[donanemab--TEMP--/treatments)--FIX-- for early AD has raised important questions about their applicability in DS-AD. Given that DS-AD is driven by [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- triplication and [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- overproduction, anti-amyloid antibodies are theoretically well-suited for this population. However, the high prevalence of CAA in DS raises concern about increased risk of [ARIA] (amyloid-related imaging abnormalities) 16(https://pubmed.ncbi.nlm.nih.gov/38513771/).
Clinical trials are underway or planned to evaluate:
- Anti-[Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- monoclonal antibodies in DS (NCT04482413 and others)
- [BACE1[/entities/[bace1[/entities/[bace1[/entities/[bace1--TEMP--/entities)--FIX--.
¶ Cholinesterase Inhibitors
[Cholinesterase inhibitors[/entities/[cholinesterase-inhibitors[/entities/[cholinesterase-inhibitors[/entities/[cholinesterase-inhibitors--TEMP--/entities)--FIX-- ([donepezil[/entities/[donepezil[/entities/[donepezil[/entities/[donepezil--TEMP--/entities)--FIX--, [rivastigmine[/treatments/[rivastigmine[/treatments/[rivastigmine[/treatments/[rivastigmine--TEMP--/treatments)--FIX--, [galantamine[/treatments/[galantamine[/treatments/[galantamine[/treatments/[galantamine--TEMP--/treatments)--FIX-- and [memantine[/treatments/[memantine[/treatments/[memantine[/treatments/[memantine--TEMP--/treatments)--FIX-- are used off-label for DS-AD, though evidence of efficacy is limited. The [cholinergic system] is affected in DS-AD similarly to sporadic AD, with degeneration of the [nucleus basalis of Meynert[/brain-regions/[nucleus-basalis-of-meynert[/brain-regions/[nucleus-basalis-of-meynert[/brain-regions/[nucleus-basalis-of-meynert--TEMP--/brain-regions)--FIX-- 1(https://pubmed.ncbi.nlm.nih.gov/34687637/).
¶ Emerging Approaches
- Antisense oligonucleotides (ASOs): [ASO therapy[/treatments/[antisense-oligonucleotide-therapy[/treatments/[antisense-oligonucleotide-therapy[/treatments/[antisense-oligonucleotide-therapy--TEMP--/treatments)--FIX-- targeting [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- mRNA to reduce [Aβ[/entities/[amyloid-beta[/entities/[amyloid-beta[/entities/[amyloid-beta--TEMP--/entities)--FIX-- production is under investigation as a DS-specific strategy
- [mTOR[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration[/mechanisms/[mtor-neurodegeneration--TEMP--/mechanisms)--FIX-- inhibitors: Rapamycin analogs to restore [autophagy[/entities/[autophagy[/entities/[autophagy[/entities/[autophagy--TEMP--/entities)--FIX-- function
- Antioxidant strategies: Targeting [oxidative stress[/mechanisms/[oxidative-stress[/mechanisms/[oxidative-stress[/mechanisms/[oxidative-stress--TEMP--/mechanisms)--FIX-- pathways to reduce cumulative oxidative damage
- [Immunotherapy[/treatments/[immunotherapy[/treatments/[immunotherapy[/treatments/[immunotherapy--TEMP--/treatments)--FIX-- approaches targeting specific tau epitopes
¶ Differences from Sporadic Alzheimer's Disease
| Feature | DS-AD | Sporadic AD |
|---|---|---|
| Age of amyloid onset | Teens–20s | 50s–60s |
| Age of clinical dementia | 50s | 70s–80s |
| Genetic driver | [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- triplication (100% penetrance) | Multifactorial (APOE4 major risk) |
| CAA prevalence | >90% | ~80% at autopsy |
| Initial amyloid deposition | Striatum, then [cortex[/brain-regions/[cortex[/brain-regions/[cortex[/brain-regions/[cortex--TEMP--/brain-regions)--FIX-- | Precuneus/medial [cortex[/brain-regions/[cortex[/brain-regions/[cortex[/brain-regions/[cortex--TEMP--/brain-regions)--FIX-- |
| Seizure prevalence | 50–75% | ~10–20% |
| neuroinflammation timing | From early life | Concurrent with pathology |
| Oxidative stress | Lifelong (SOD1 triplication) | Age-associated |
¶ Research and Clinical Trials
The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS) is the largest longitudinal biomarker study in DS, following over 400 adults with DS across multiple US sites. ABC-DS has been instrumental in characterizing the temporal sequence of biomarker changes in DS-AD and is providing critical data for clinical trial design 1(https://pubmed.ncbi.nlm.nih.gov/34687637/).
The LIFE-DSR (Longitudinal Investigation for Enhancing Down Syndrome Research) study is another major initiative that collects longitudinal natural history data to support clinical trial readiness. These studies collectively demonstrate that DS represents an ideal population for AD prevention trials due to the predictable disease course, identifiable at-risk population, and available biomarkers 16(https://pubmed.ncbi.nlm.nih.gov/38513771/).
The 2025 Lancet Neurology review by Rafii et al. synthesized the current state of knowledge on DS-AD biomarkers, clinical symptoms, and pathology, establishing DS-AD as a recognized genetic form of AD comparable to autosomal dominant AD caused by [PSEN1[/genes/[psen1[/genes/[psen1[/genes/[psen1--TEMP--/genes)--FIX--, [PSEN2[/genes/[psen2[/genes/[psen2[/genes/[psen2--TEMP--/genes)--FIX--, or [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX-- mutations 17(https://pubmed.ncbi.nlm.nih.gov/40818475/).
¶ See Also
- [Neurodegenerative Diseases Index[/[diseases[/[diseases[/[diseases[/[diseases[/[diseases[/diseases
- [Antisense Oligonucleotide (ASO) Therapy in Neurodegeneration[/treatments/[antisense-oligonucleotide-therapy[/treatments/[antisense-oligonucleotide-therapy[/treatments/[antisense-oligonucleotide-therapy--TEMP--/treatments)--FIX--
- [Galantamine[/treatments/[galantamine[/treatments/[galantamine[/treatments/[galantamine--TEMP--/treatments)--FIX--
- [Immunotherapy for Neurodegenerative Diseases[/treatments/[immunotherapy[/treatments/[immunotherapy[/treatments/[immunotherapy--TEMP--/treatments)--FIX--
- [Memantine[/treatments/[memantine[/treatments/[memantine[/treatments/[memantine--TEMP--/treatments)--FIX--
¶ Background
The study of Down Syndrome And Alzheimer's Disease has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
¶ External Links
- PubMed - Biomedical literature
- Alzheimer's Disease Neuroimaging Initiative - Research data
- Allen Brain Atlas - Brain gene expression data
¶ References
- [Fortea J, Vilaplana E, Carmona-Iragui M, et al. Alzheimer's Disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021;20(11):930-942. . PMID: 34687637)
- [Doran E, Keator D, Head E, et al. Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer's Disease: The Role of [APP[/genes/[app[/genes/[app[/genes/[app--TEMP--/genes)--FIX--. J Alzheimers Dis. 2017;56(2):459-470. . PMID: 27983553)
- [Antonarakis SE, Skotko BG, Rafii MS, et al. Down syndrome. Nat Rev Dis Primers. 2020;6(1):9. . PMID: 32029743)
- [Head E, Lott IT. Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology. Curr Alzheimer Res. 2016;13(1):18-29. . PMID: 26651341)
- [Hamlett ED, Goetzl EJ, Ledreux A, et al. Exosomal biomarkers in Down syndrome and Alzheimer's Disease. Free Radic Biol Med. 2018;114:110-121. . PMID: 28882786)
- . PMID: 28807816
- [Perluigi M, Di Domenico F, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer's Disease. Physiol Rev. 2024;104(1):103-197. . PMID: 32775597)
- [Barone E, Head E, Butterfield DA, Perluigi M. HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer's Disease neuropathology. Free Radic Biol Med. 2017;111:262-269. . PMID: 27838436)
- [Head E, Phelan MJ, Doran E, et al. Down syndrome, Alzheimer's Disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis. Dev Neurobiol. 2019;79(7):716-737. . PMID: 31278851)
- [Petersen ME, Rafii MS, et al. Association of biological sex with clinical outcomes and biomarkers of Alzheimer's Disease in adults with Down syndrome. Brain Commun. 2023;5(3):fcad108. . PMID: 37056479)
- [Perluigi M, Di Domenico F, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer's Disease. Physiol Rev. 2024;104(1):103-197. . PMID: 37843394)
- [Lleó A, Fortea J, et al. Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer's Disease. Nat Commun. 2025;16:61054. DOI: 10.1038/s41467-025-61054-z)
- [Santoro JD, Filipink RA, Gatzke AM, et al. Neurologic complications of Down syndrome: a systematic review. J Neurol. 2021;268:4495-4509. . PMID: 32920658)
- [Carmona-Iragui M, et al. Blood Biomarkers for Alzheimer's Disease in Down Syndrome. J Clin Med. 2021;10(16):3639. . PMID: 34441934)
- [Zhou Y, et al. Blood-based biomarkers for Alzheimer's Disease in Down syndrome: A systematic review and meta-analysis. Alzheimers Dement. 2025. . PMID: 40219863)
- [Sokol DK, et al. Alzheimer's drugs, APPlication for Down syndrome? Ageing Res Rev. 2024;95:102247. . PMID: 38513771)
- [Rafii MS, et al. Down syndrome and Alzheimer's Disease: insights into biomarkers, clinical symptoms, and pathology. Lancet Neurol. 2025;24(9):831-846. . PMID: 40818475)