Parvalbumin interneurons (PV interneuron) connect to excitatory neurons in the forebrain (top). In healthy individuals (control; left), the NPTX2 protein (red) arranges GluA4-containing AMPA receptors (blue) in clusters at these connections. As a result, electrical signals from the excitatory neurons strongly activate the interneurons. A sodium channel called Nav1.1 (black) in the interneurons helps to generate electrical signals that inhibit other neurons in the circuit. In the brains of individuals with Alzheimer’s disease (right), the levels of NPTX2, GluA4 and Nav1.1 are all lower than in healthy individuals; this leads to less inhibitory interneuron activity. Other neurons in the circuit thus become more active than they should be, resulting in defects in circuit function and cognitive impairments. NPTX2 can also be detected in the cerebrospinal fluid (CSF; bottom). Individuals with Alzheimer’s disease (right) have less NPTX2 in their CSF compared to healthy individuals (control; left). NPTX2 levels in CSF correlate with cognitive impairments.
IMAGE CREDIT: JE Hanson, A Bruce.