This finding may explain the seemingly conflicting results presented herein regarding protein levels of INPP5D in the AD brain: full-length aqueous-soluble INPP5D was dramatically reduced in the AD brain, and the elevation in INPP5D observed by immunostaining may reflect the presence of truncated and functionally inactive INPP5D protein generated from the isoforms lacking the phosphatase domain. Here, INPP5D is linked to Alzheimer disease.