Lipoprotein(a) levels in Down syndrome: A conundrum

Topic: Brain proteins, microglia and lab models

Introduction Lipoprotein a (Lp(a)) is a low-density lipoprotein (LDL)-like particle that has been associated with risk for vascular inflammation, atherogenesis, calcification, and thrombosis in the general population but is also a risk factor for Alzheimer disease (AD). Objective The aim of this study was to conduct a retrospective study of lipoprotein a, Lp(a), levels in adults with Down syndrome (DS) and at risk for Alzheimer's disease (AD). Methods Lp(a) serum concentrations were collected from 96 adults as part of a routine clinical assessment. A comprehensive medical chart review was conducted, including clinical laboratory values that could contribute to cognitive dysfunction (e.g., thyroid function tests, C-reactive protein(CRP), vitamin B12, lipid profiles, and vitamin D levels). Generalized linear regression models were constructed to quantify the relationship between each medical condition or laboratory value and Lp(a) level. Results There was insufficient evidence for an increased risk for earlier age of onset of AD in those with elevated Lp(a) plasma levels (≥50 mg/dL). Discussion Adults with DS may have unique neuro- and cardio- protective factors that deserve future investigation. Highlights Lipoprotein a (Lp(a)) elevations in Down syndrome (DS) are not associated with higher risk for Alzheimer's disease (AD). Lp(a) elevations are not associated with typical vascular risk factors in DS. Distinct neuro- and cardio- protective factors may play a role in DS that may provide novel insights.

Key findings

• Introduction Lipoprotein a (Lp(a)) is a low-density lipoprotein (LDL)-like particle that has been associated with risk for vascular inflammation, atherogenesis, calcification, and thrombosis in the general population but is also a risk factor for Alzheimer disease (AD).
• Results There was insufficient evidence for an increased risk for earlier age of onset of AD in those with elevated Lp(a) plasma levels (≥50 mg/dL).
• Highlights Lipoprotein a (Lp(a)) elevations in Down syndrome (DS) are not associated with higher risk for Alzheimer's disease (AD).
• Lp(a) elevations are not associated with typical vascular risk factors in DS.

Why it matters

In 96 adults with Down syndrome, elevated lipoprotein(a) levels were not associated with an earlier age of Alzheimer's disease onset. This retrospective study found no evidence of increased risk and does not test any treatment, cure or prevention.

Study details

• Participants96
• Evidence strengthLow

Read the original

• DOI: 10.1002/alz.70338
• PubMed: 40474237
• Original source →
• Free full text: Alzheimer s & Dementia →

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

@article{rosas2025-40474237,
  author  = {Rosas, H. D. and Lai, F. and Mercaldo, N.},
  title   = {{Lipoprotein(a) levels in Down syndrome: A conundrum}},
  journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
  year    = {2025},
  doi     = {10.1002/alz.70338},
  pmid    = {40474237},
  url     = {https://doi.org/10.1002/alz.70338}
}

Studies this one cites

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

• Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome JAMA network open · 2022-05-02 · usefulness score 78/100 · Disparities
• Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study Lancet (London, England) · 1997-01-01 · usefulness score 62/100 · How common it is
• Cerebrovascular pathology in Down syndrome and Alzheimer disease Acta neuropathologica communications · 2017-12-01 · usefulness score 51/100 · Down syndrome and Alzheimer's
• Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis Journal of neuroinflammation · 2013-07-16 · usefulness score 47/100 · Down syndrome and Alzheimer's

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• Phospholipid composition and levels are altered in Down syndrome brain Brain research · 2000-06-01 · usefulness score 42/100
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• Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms? Clinica chimica acta; international journal of clinical chemistry · 2004-03-01 · usefulness score 41/100
• Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology Naunyn-Schmiedeberg's archives of pharmacology · 2001-02-01 · usefulness score 40/100

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