Test Code: 2199

Alzheimer and dementia: Deletion/Duplication Panel
Test Code: 2199
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
TREM2

INDICATIONS
The test is indicated for:

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

METHODOLOGY
DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.

DETECTION
Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

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

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection 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.