Amyloid Beta (Aβ) Precursor Protein (APP), Full Gene Sequencing

CPT Code(s): 81406

Ordering Recommendation: APP full gene sequencing is recommended for individuals with clinical symptoms of early-onset Alzheimer's disease, which begins before are 65, and individuals with a positive family history of early-onset Alzheimer's disease.

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: It should be noted that only the coding and immediate flanking regions of the APP gene are analyzed by DNA sequencing. Changes in the promoter region and other non-coding regions will therefore not be detected by our assay. In addition, the presence of a large intragenic deletion of the APP gene (such as the deletion of an exon) will not be detected by sequence analysis. All results should be interpreted in context of clinical findings, relevant history, and other laboratory data.

References: Gene Reviews