title: Inverse association of Pin1 and tau accumulation in Alzheimer's disease hippocampus.
abstract: Neurofibrillary degeneration, one of the pathological hallmarks of Alzheimer's disease, is not ubiquitous to all brain regions or neurons. While a high degree of vulnerability has been documented for entorhinal cortex, hippocampal and neocortical pyramidal neurons other brain structures are largely spared. Even within highly vulnerable regions such as hippocampus neurons are affected to a variable extent. The molecular basis for this selective susceptibility remains unknown. Neurofibrillary degeneration involves hyperphosphorylation of tau which critically impairs its binding capacity to microtubule and, therefore, is believed to disrupt the axonal cytoskeleton. Recently, Lu et al. [Nature (1999) 399:784] described the ability of the peptidyl-prolyl cis-trans isomerase Pin1 to recover microtubule-binding affinity and microtubule stabilisation of phosphorylated tau. In the present study, we analysed the potential involvement of Pin1 in selective vulnerability of hippocampal neurons to neurofibrillary degeneration in Alzheimer's disease. Pin1 immunoreactivity appeared as cytoplasmic granules affecting hippocampal subfields to a different extent (CA2>subiculum>CA1>CA3/CA4). Since the main markers of granulovacuolar degeneration do not co-label Pin1-immunoreactive granules, we propose that these granules may represent a new lesion in Alzheimer's disease. Neurons containing Pin1 granules were devoid of neurofibrillary tangles. Granular accumulation of Pin1 may correspond to an absence of neurofibrillary lesions in these cells and might be associated with other mechanisms of neuronal degeneration.
authors.affiliation: Department of Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Holzer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gärtner
authors.forename: Andrea
authors.initials: A
authors.lastname: Stöbe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.forename: Hildegard
authors.initials: H
authors.lastname: Gruschka
authors.forename: Martina K
authors.initials: MK
authors.lastname: Brückner
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis*; D010766:Phosphorylation; D016875:tau Proteins / Q000096:biosynthesis*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016875:tau Proteins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase