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When an Alzheimer stem says early onset plus a strong vertical family history, move from common late-life risk to rare single-gene disease. For example, a 48-year-old with an affected parent and grandparent is not an APOE screening vignette. PSEN2 sits in the small causative-gene drawer with APP and PSEN1.

Pathogenic PSEN2 variants alter presenilin biology and are recognised causes of autosomal dominant early-onset familial Alzheimer disease. The exam distinction is causative familial disease versus APOE-style susceptibility for common late-onset Alzheimer disease. Clinical implications: a pathogenic PSEN2 result changes the counselling frame for relatives.

Look for dementia before 60 to 65 years, multiple affected relatives, vertical transmission, and a panel result naming presenilin 2.

• PSEN2 vs APOE e4, PSEN2 is a causative early-onset familial Alzheimer gene, whereas APOE e4 is a susceptibility allele.
• PSEN2 vs APP, both can cause familial Alzheimer disease, but APP is the amyloid precursor protein gene on chromosome 21.
• PSEN2 vs MAPT or GRN, PSEN2 points to Alzheimer disease, unlike MAPT/GRN stems that point toward frontotemporal dementia.

Trap, treating every Alzheimer gene as a risk allele. Resolution: APP, PSEN1 and PSEN2 are the causative early-onset familial Alzheimer genes.

Trap, choosing APP whenever amyloid is mentioned. Resolution: APP is one member of the triad; presenilin clues point to PSEN1 or PSEN2.

First decide whether the question is asking causation or risk. If the stem gives a pathogenic familial variant, answer with autosomal dominant causation. If it gives APOE, answer risk susceptibility. In practice, this keeps counselling-style genetics separate from ordinary late-onset risk-factor teaching.