Test Code: 2196

Alzheimer and dementia: Sequencing Panel
Test Code: 2196
Turnaround time: 7 weeks

CONDITION DESCRIPTION
Alzheimer disease (AD) is characterized by dementia that usually begins with subtle and poorly recognized memory failure which slowly becomes progressive and inevitably incapacitating; and is consistent with the accumulation of β-amyloid plaques and intraneuronal neurofibrillary tangles . Other symptoms such as poor judgment, language disturbance, confusion, withdrawal, agitation and hallucinations are associated with AD. Frequently occurring with AD are myoclonus incontinence, mutism, increased muscle tone, seizures and Parkinsonian features. Death from AD is a consequence of malnutrition, pneumonia and general inanition.

The clinical duration of AD is 8 to 10 years, with an estimated range of one to twenty five years. About 25% of all AD is familial, of which about 95% is late onset (age > 60-65 years) and with 5% as early onset (age < 65 years).

The prevalence of AD increases with age with about 10% of persons older than 70 years having significant memory loss and with about 50% of these individuals having AD. About 25-45% of persons older than 85 years have dementia. The incidence of AD increases from 2.8 in 1,000 persons in the 65-69 year age group, to 56.1 in 1,000 persons older than 90 years (Kukull et al., 2002).

The association of the APOE e4 allele and mutations in SORL1, PRNP and TREM2 are identified in late-onset AD, while mutations in APP, PSEN1 and PSEN2 are present in early-onset AD.

References:

  • Gene Reviews
  • Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, van Belle G, Jolley L, Larson EB. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol. 2002;59:1737–46.
  • Golanska E, Hulas-Bigoszewska K, Sieruta M, Zawlik I, Witusik M, Gresner SM, Sobow T, Styczynska M, Peplonska B, Barcikowska M, Liberski PP, Corder EH. Earlier onset of Alzheimer’s disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. J Alzheimers Dis. 2009;17(2):359-68.

GENES
APOE, APP, PRNP, PSEN1, PSEN2, SORL1, TREM2

INDICATIONS
The test is indicated for:

  • Individuals with a clinical or suspected diagnosis of Alzheimer and dementia.

METHODOLOGY
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

DETECTION
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.
Analytical Sensitivity: ~99%.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types:

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) tube:
Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements:
In microtainer: 60 μg.
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.