P-NfL segregates depression from dementia in older individuals, and while only mildly elevated in patients with AD, it is an efficient marker for ruling out underlying neurodegeneration.20,21 P-NfL is also high in amyotrophic lateral sclerosis (ALS), atypical parkinsonian disorders, frontotemporal dementia, and in patients with Down syndrome with AD, providing evidence of an underlying neurodegenerative cause of a patient's symptoms.21, -, 23. This evidence concerns the gene NEFL and Down syndrome.