WBR0313
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Neurology, SubCategory::General Principles |
| Prompt | [[Prompt::A 40 year old male with Down syndrome is brought to his primary care physician by an employee of his assisted care facility for cognitive decline below his baseline over the past year. He has increasingly forgotten where his room is and is unable to recognize staff he used to know well. Which of the following genes/proteins is most likely responsible for predisposing the patient to the syndrome he has developed?]] |
| Answer A | AnswerA::Presenilin |
| Answer A Explanation | AnswerAExp::'''Incorrect:''' Mutations in the genes encoding the Presenilin proteins cause early onset forms of familial Alzheimer’s disease. However, presinilin mutations are not associated with Down syndrome. |
| Answer B | AnswerB::Apolipoprotein E |
| Answer B Explanation | [[AnswerBExp::Incorrect: The E4 variant of Apoplipoprotein R is the largest known genetic risk factor for late-onset sporadic Alzheimer’s disease. Carriers of 2 APOE4 alleles have a 20 fold increased risk of Alzheimer’s disease compared to non-carriers. APOE allele status is not related to Down syndrome.]] |
| Answer C | AnswerC::Alpha synuclein |
| Answer C Explanation | AnswerCExp::'''Incorrect:''' Alpha synuclein is a protein which aggregates intracellularly to form the Lewy bodies associated with Parkinson’s disease and Lewy body dementia. Abnormalities of alpha synuclein are not associated with Down syndrome. |
| Answer D | AnswerD::Tau |
| Answer D Explanation | [[AnswerDExp::Incorrect: Hyperphosphorylated tau composes the pathological neurofibrillary tangles which dot the brains of Alzheimer’s patients. Tau protein abnormalities are not thought to be the driving force behind the accelerated development of Alzheimer’s disease associated with Down Syndrome.]] |
| Answer E | AnswerE::Amyloid precursor protein |
| Answer E Explanation | AnswerEExp::'''Correct:''' The amyloid precursor protein lies on chromosome 21. An extra copy of this gene in Alzheimer’s patients is likely responsible for the accelerated development of Alzheimer’s disease in Down syndrome patients. |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::The patient in this vignette is suffering from early onset Alzheimer’s disease. Patients with Down syndrome have a higher risk of developing early onset Alzheimer’s disease. This increased risk is thought to be caused by an extra copy of the gene encoding the amyloid precursor protein (APP). The increased copy of APP causes more APP to be made. Amyloid precursor protein is cleaved to generate Beta-amyloid. Aggregates of beta amyloid compose the amyloid plaques that are a pathologic hallmark of Alzheimer’s disease. The processing of APP into beta amyloid is presented below.
 Educational Objective: The amyloid precursor protein lies on chromosome 21. An extra copy of this gene in Alzheimer’s patients is likely responsible for the accelerated development of Alzheimer’s disease in Down syndrome patients. References: First Aid 2012 page 465 |
| Approved | Approved::Yes |
| Keyword | |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |