Affiliations: [a]
Laboratory for Alzheimer’s Disease & Aging Research, VA Medical Center, Kansas City, MO, USA
| [b]
Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA
| [c]
Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
| [d]
The University of Kansas Alzheimer’s Disease Center, Kansas City, KS, USA
Correspondence:
[*]
Correspondence to: William Z. Suo, Laboratory for Alzheimer’s Disease & Aging Research, Veterans Affairs Medical Center, 4801 E. Linwood Blvd., Kansas City, MO 64128, USA. Tel.: +1 816 861 4700 ext. 58270; Fax: +1 816 922 4667; E-mail: William.Suo@va.gov.
Abstract: Prevention of Alzheimer’s disease (AD) is a high priority mission while searching for a disease modifying therapy for AD, a devastating major public health crisis. Clinical observations have identified a prodromal stage of AD for which the patients have mild cognitive impairment (MCI) though do not yet meet AD diagnostic criteria. As an identifiable transitional stage before the onset of AD, MCI should become the high priority target for AD prevention, assuming successful prevention of MCI and/or its conversion to AD also prevents the subsequent AD. By pulling this string, one demonstrated cause of amnestic MCI appears to be the deficiency of G protein-coupled receptor-5 (GRK5). The most compelling evidence is that GRK5 knockout (GRK5KO) mice naturally develop into aMCI during aging. Moreover, GRK5 deficiency was reported to occur during prodromal stage of AD in CRND8 transgenic mice. When a GRK5KO mouse was crossbred with Tg2576 Swedish amyloid precursor protein transgenic mouse, the resulted double transgenic GAP mice displayed exaggerated behavioral and pathological changes across the spectrum of AD pathogenesis. Therefore, the GRK5 deficiency possesses unique features and advantage to serve as a prophylactic therapeutic target for MCI due to AD.
