Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with severe memory loss and impaired cognitive skills. A common pathological change found in AD-affected brains is the accumulation of a peptide named amyloid-β (Aβ) that can form plaques. Aβ aggregates are visible to structural scanning tools; however, these bulky and expensive instruments are accessible to trained personnel in clinical settings only, thus hampering timely diagnosis of the disease, particularly in low-resource settings. In this work, we design an organic electrochemical transistor (OECT) for in vitro detection of Aβ aggregates in human serum. The OECT channel is integrated with a nanostructured isoporous membrane which has a strong affinity for Aβ aggregates. The detection mechanism relies on the membrane capturing Aβ aggregates larger than the size of its pores and thus blocking the penetration of electrolyte ions into the channel underneath. Combining the high transconductance of the OECT with the precise porosity and selectivity of the membrane, the device detects the presence of Aβ aggregates in human serum samples with excellent sensitivity. This is the first-time demonstration of a biofunctionalized, nanostructured, and isoporous membrane integrated with a high-performance transistor for biosensing. This robust, low-power, non-invasive, and miniaturized sensor aids in the development of point-of-care tools for early diagnosis of AD.