Mechanisms
Elevated Lp(a) does not predict earlier Alzheimer's onset in adults with Down syndrome, hinting at unique protective factors, 96-patient study finds (Alzheimers Dement 2025)
Original title: Lipoprotein(a) levels in Down syndrome: A conundrum
This retrospective study collected Lp(a) serum concentrations from 96 adults with Down syndrome undergoing routine clinical assessment for Alzheimer's disease (AD) risk, alongside a comprehensive chart review of other laboratory values that could affect cognition (thyroid function, CRP, vitamin B12, lipid profiles, vitamin D). Despite Lp(a)'s established links to vascular inflammation, atherogenesis, calcification, thrombosis and AD risk in the general population, there was insufficient evidence for an earlier age of AD onset in Down syndrome adults with elevated Lp(a) (50 mg/dL or above), and Lp(a) elevation was not associated with the typical vascular risk factors seen in the general population. The authors conclude adults with Down syndrome may possess distinct neuro- and cardio-protective factors that decouple elevated Lp(a) from its usual risks, warranting further investigation into what these protective mechanisms might be.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.