Early Onset Alzheimer's NGS Diagnostic Test

Clinical Use

Use

Diagnostic testing. This test is to detect pathogenic variants in the amyloid protein precursor (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes that cause autosomal dominant early onset Alzheimer's disease. Testing may be considered to confirm a diagnosis of early onset Alzheimer's disease in symptomatic individuals and for presymptomatic testing in individuals with a family history of early onset AD or a relative with a known APP, PSEN1 or PSEN2 pathogenic variant. This testing is not appropriate for individuals under the age of 18. Alzheimer's disease (AD) is the most common form of progressive dementia and currently affects more than 5 million Americans. It is a neurodegenerative disorder with brain findings of neurofibrillary tangles and amyloid plaques. AD is a complex and heterogeneous disease, influenced by many genetic and environmental factors. Early onset AD (presenting before age 65, with cases as young as 25 and most cases between 45-60) occurs in ~5% of AD cases. Early onset familial AD comprises <2% if AD cases. Of early onset familial AD, PSEN1 contributes to the most cases (20% to 70%), followed by APP (10% to 15%) and PSEN2 (~5%). Penetrance is considered to be ~100% for APP and PSEN1 by age 60-65 and slightly reduced for PSEN2.

Special Instructions

Not provided.

Limitations

This assay may not detect mosaicism or large chromosomal aberrations such as rearrangements and inversions that do not change the copy number of genomic regions. It also does not detect repeat expansions. Results might be compromised due to factors like rare genetic variants, sex chromosome abnormalities, pseudogene interference, homologous regions, or specimen quality issues such as mislabeled samples. Interpretation is limited by the data available at the time of reporting and might change as more information becomes available.

Test Details