Elsevier

Neuroscience Letters

Volume 356, Issue 1, 6 February 2004, Pages 49-52
Neuroscience Letters

A human granin-like neuroendocrine peptide precursor (proSAAS) immunoreactivity in tau inclusions of Alzheimer's disease and parkinsonism–dementia complex on Guam

https://doi.org/10.1016/j.neulet.2003.11.028Get rights and content

Abstract

The deposition of tau inclusions is one of the neuropathological hallmarks in neurodegenerative disorders with dementia. We have reported that the N-terminal fragment of a human granin-like neuroendocrine peptide precursor (N-proSAAS) is accumulated in Pick bodies. However, it is unknown whether N-proSAAS is widely accumulated in tau inclusions in other tauopathies. Here, we performed an immunohistochemical examination using antibodies against both the N- and C-terminal sequence of proSAAS in the brains of patients with Alzheimer's disease and parkinsonism–dementia complex on Guam. The antibody against N-proSAAS immunostained neurofibrillary tangles and neuritic plaques in both diseases, whereas the antibody against the C-terminal sequence of proSAAS did not. The results of the present study suggest that N-proSAAS or proSAAS-like molecules were trapped within the tau fibrils and accumulated in tau inclusions.

Section snippets

Acknowledgements

The authors thank Dr L.D. Fricker, Albert Einstein College of Medicine, for providing the anti-N- and C-proSAAS antibodies.

Cited by (22)

  • Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction

    2021, Molecular Therapy Nucleic Acids
    Citation Excerpt :

    ProSAAS, encoded by gene Pcsk1n, an abundant secretory polypeptide that is widely expressed in the human, mouse, and rat brain, regulates the proteolytic cleavage of neuroendocrine peptide precursors. ProSAAS has been widely suggested to colocalize with Lewy bodies or amyloid plaques and carry out chaperone anti-aggregant functions in AD, Pick’s disease, and Parkinsonism-dementia (Figure 10),42–47 contribute to the physiological effects of psychostimulants,48 and serve as a therapeutic agent in the case of food-intake disorders49,50 as well as a cerebrospinal fluid biomarker in AD and frontotemporal dementia.51,52 It has been previously reported that Pcsk1n expression was upregulated in the hippocampus of rats with more severe BBB disruption;53 however, the role of ProSAAS in BBB regulation in mice has remained obscure.

  • Granins as disease-biomarkers: Translational potential for psychiatric and neurological disorders

    2010, Neuroscience
    Citation Excerpt :

    In addition to neurological, psychiatric and clinical diagnoses, altered levels of tau and amyloid fragments in CSF are routinely used for diagnostic purposes, although their diagnostic performance is not optimal with regard to specificity (Blennow et al., 2006; Sonnen et al., 2008). Several studies identified increased CgA, SgII and ProSAAS, in post-mortem filament aggregates in tauopathies (Weiler et al., 1990; Munoz, 1991; Kikuchi et al., 2003; Wada et al., 2004; Lechner et al., 2004), and one proteomic study identified a decreased CgA level in the CSF of canonical but not late onset Type II (Kamboh, 2004) Alzheimer's disease patients (Blennow et al., 1995, but see O'Connor et al., 1993). More recently, several proteomic studies have confirmed the potential utility of granin fragments as candidate diagnostic biomarkers for tauopathies.

View all citing articles on Scopus
View full text