Genetic overlap between schizophrenia spectrum disorders and Alzheimer's disease: Current evidence and future directions - An integrative review

Schizophrenia and Alzheimer's disease (AD) are distinct neurodegenerative disorders characterized by progressive cognitive deficits and structural alterations in the brain. Schizophrenia typically emerges in adolescence or early adulthood with symptoms such as hallucinations, delusions, and cognitive impairments, whereas AD primarily affects elderly individuals, causing progressive memory loss, cognitive decline, and behavioral changes. Delusional disorder, which often emerges later in life, shares some features with schizophrenia and is considered a schizophrenia spectrum disorder. Patients with schizophrenia or delusional disorder, particularly women and those aged 65 years or older, have an increased risk of developing AD later in life. In contrast, approximately 30 % of AD patients exhibit psychotic symptoms, which accelerate cognitive decline and worsen health outcomes. This integrative review explored the genetic overlap between schizophrenia spectrum disorders and AD to identify potential shared genetic factors. The genetic correlations between schizophrenia and AD were weak but positive (r(g)=0.03-0.10). Polygenic risk scores (PRSs) for schizophrenia and AD indicate some genetic predisposition, although findings are inconsistent among studies; e.g., PRS-schizophrenia or PRS-AD were associated with the risk of developing psychosis in patients with AD. A higher PRS for various developmental and psychiatric disorders was correlated with an earlier age at onset of schizophrenia. Research gaps include the need for studies on the impacts of PRS-AD on the risk of schizophrenia, genetic correlations between later-onset delusional disorder and AD, and genetic relationships between AD and late-onset schizophrenia (LOS) with a greater risk of progressing to AD. Further investigation into these genetic overlaps is crucial to enhance prevention, treatment, and prognosis for affected patients.