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Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome

Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T‐lymphocyte interphases from individuals with Down syndrome (DS) with and without “mild cognitive impairment” (MCI‐DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI‐DS in this high‐risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI‐DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18‐month intervals with clinical and telomere assessments: (1) MCI‐DS group data were collected approximately three years prior to development of MCI‐DS; (2) 18 months later; (3) when MCI‐DS was first observed. These telomere measures were compared to those from another 10 adults with DS matched by sex and approximate age but without indications of MCI‐DS (Controls). PNA (peptide nucleic acid) probes for telomeres together with a chromosome two centromere probe were used. Findings indicated telomere shortening over time for both Cases and Controls. Group differences emerged by 18‐months prior to recognition of MCI‐DS onset and completely non‐overlapping distributions of telomere measures were observed by the time of MCI‐DS onset. This study adds to accumulating evidence of the value of telomere length, as an early biomarker of AD progression in adults with Down syndrome.