title: Elevated Tau Level in Aged Rat Cerebrospinal Fluid Reduced by Treatment with a Neurotrophic Compound.
abstract: Alzheimer's disease (AD) is the single major cause of dementia in middle- to old-age individuals, and, as of yet, no disease-modifying therapeutic drug is available for its treatment. A major obstacle in the successful development of disease-modifying therapeutic drugs has been the lack of suitable animal models of the sporadic form of AD as well as a biomarker that can be used both for therapeutic preclinical studies and for human clinical trials. Previously we showed neurogenesis and neuronal plasticity deficits and cognitive impairment and their rescue with a neurotrophic peptidergic compound, DGGLAG named P021, in aged Fisher rats. Here we show that P021 is blood-brain-barrier-permeable, and chronic oral treatment with this compound can reduce the brain level of total tau in the aged rats. Furthermore, cerebrospinal fluid (CSF) levels of both tau and Aβ/AβPP are elevated in the aged animals, and chronic treatment with P021 can reduce tau but not Aβ/AβPP to that of the levels found in young adult rats. Importantly, P021 does not induce any detectable immune reaction in rats. Collectively, these studies show the therapeutic potential of P021 as a disease-modifying compound and the suitability of the aged Fisher rats as a model of cerebral aging in which the therapeutic efficacy of a tau-reducing compound can be monitored in the CSF.
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Sabiha
authors.initials: S
authors.lastname: Khatoon
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chalbot
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolognin
authors.forename: Jukka
authors.initials: J
authors.lastname: Puoliväli
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000375:Aging; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000134:cerebrospinal fluid; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C054369:MAPT protein, human; C489131:Mapt protein, rat; D018697:Nootropic Agents; D009842:Oligopeptides; C000608789:P021 peptide; D011994:Recombinant Proteins; D016875:tau Proteins; D000218:Adamantane
keywords: Aged Fisher rat; Alzheimer’s disease; ELISA; cerebral aging; cerebrospinal fluid; rat; tau protein