A study in a FAD mouse model, which knocked out the NfL gene, showed that NfL deficiency significantly increased AD-related neurodegeneration, a finding that might suggest a role for NfL in maintaining neuronal structure in patients with AD.31 Moreover, in APP/PS1 mice, histopathologic examination found NfL-positive neuritic abnormalities, consistent with increased NfL in AD, signifying underlying axonal damage.10 The same study showed serum NfL concentrations increased early in the disease and were closely associated with progression of AD-like pathology. This evidence concerns the gene APP and Alzheimer disease.