Amyloid Beta (Aβ) Precursor Protein (APP), Targeted Variant Sequencing

CPT Code(s): 81404

Ordering Recommendation: Targeted APP sequencing is recommended for individuals with clinical symptoms of early-onset Alzheimer's disease, which begins before age 65 and 1) where either the familial variant is known or 2) the variant has been identified by a research protocol and needs to be confirmed in a clinical laboratory.

Synonyms: APP, Amyloid beta precursor protein, Aβ, Alzheimer's disease, early onset Alzheimer's disease, early-onset, dementia, cerebral amyloid angiopathy, Alzheimer

Methodology: Sanger sequence analysis. The APP cDNA reference sequence used is NM_000484.4.

Performed: Monday-Friday

Reported: 14 days

Collect: Preferred: whole blood in a lavender top (EDTA) tubes, cultured and uncultured cells

Specimen Volume: Blood: 3 mL whole blood (minimum 1 mL)

Storage/Transport: Refrigerated/Room temperature

Unacceptable Conditions: Grossly hemolyzed or clotted 

Stability: One month refrigerated; one month frozen

Reference Interval: By report

Characteristics: Alzheimer's disease (AD) is characterized by dementia that typically begins with subtle and poorly recognized failure of memory (often called mild cognitive impairment or MCI) and slowly becomes more severe and, eventually, incapacitating. Other common findings include confusion, poor judgment, language disturbance, visual complaints, agitation, withdrawal, and hallucinations. The typical clinical duration of the disease is eight to ten years, with a range from one to 25 years. Approximately 5% of Alzheimer's disease is early onset (age<60-65).

Inheritance: Autosomal dominant

Cause: APP is responsible for less than 10-15% of all early-onset Alzheimer disease.

Incidence: Rare

Penetrance: 100%

Analytical sensitivity and specificity: 99%

Limitations:  Only the targeted variant of the APP gene is analyzed by DNA sequencing.  All results should be interpreted in context of clinical findings, relevant history, and other laboratory data. 

References: Gene Reviews