Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies

Pankajavalli Ramakrishnan, Dennis W Dickson, Peter Davies

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Pin1, a peptidyl-prolyl isomerase binds to mitotic serine or threonine phosphoproteins. In Alzheimer's disease (AD) evidence points to the reactivation of mitosis in vulnerable neurons. Tangles composed of hyperphosphorylated tau contain phosphorylated Thr231 (pThr 231 tau), which occurs to a greater extent in the AD brain than in the normal brain, and Pin1 has been shown to bind pThr231 tau. Here, Pin1 distribution in AD, and its colocalization with pThr231 tau in AD, FTDP-17 (P301L), Pick's disease (PiD), and PSP was investigated using TG-3, a monoclonal antibody to conformationally altered pThr231 tau. The Pin1 antibody A-20 detected granular Pin1 staining in AD brains, but not in normal brains. A-20 immunoreactive granules colocalized with TG-3-stained granules but not with TG-3-stained pretangles, tangles, or Pick bodies in AD, PiD, and FTDP-17 (P301L). Pin1 granules were sparse in PSP, and rarely did A-20 colocalize with TG-3. The appearance of Pin1 granules in the early stages of AD, PiD, and FTDP-17 (P301L) implicates Pin1 in their pathogenesis but not in PSP.

Original languageEnglish (US)
Pages (from-to)251-564
Number of pages314
JournalNeurobiology of Disease
Volume14
Issue number2
DOIs
StatePublished - Nov 2003

Fingerprint

Tauopathies
Alzheimer Disease
Pick Disease of the Brain
Frontotemporal Dementia
Brain
Peptidylprolyl Isomerase
Phosphoproteins
Threonine
Mitosis
Serine
Monoclonal Antibodies
Staining and Labeling
Neurons
Antibodies

Keywords

  • Alzheimer's disease
  • Neurodegeneration
  • Pin1
  • Tau
  • Tauopathies

ASJC Scopus subject areas

  • Neurology

Cite this

Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies. / Ramakrishnan, Pankajavalli; Dickson, Dennis W; Davies, Peter.

In: Neurobiology of Disease, Vol. 14, No. 2, 11.2003, p. 251-564.

Research output: Contribution to journalArticle

Ramakrishnan, Pankajavalli ; Dickson, Dennis W ; Davies, Peter. / Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies. In: Neurobiology of Disease. 2003 ; Vol. 14, No. 2. pp. 251-564.
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