Loma Linda University

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Salvador Soriano Castell, PhD
Associate Professor, Pathology and Human Anatomy
School of Medicine
Associate Professor, Basic Sciences
School of Medicine
Member, Anatomy, SM, Faculty of Graduate Studies
Publications    Scholarly Journals--Published
  • Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Morihara T, Takeda M.  (2010). KIBRA Genetic Polymorphism Influences Episodic Memory in Alzheimer’s Disease, but Does Not Show Association with Disease in a Japanese Cohort. Dement Geriatr Cogn Disord 30(4):302-8 2010 ( 1/2010 - 8/2012 )
    BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer''s disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.
  • Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography. Canuet L, Ishii R, Iwase M, Ikezawa K, Kurimoto R, Takahashi H, Currais A, Azechi M, Aoki Y, Nakahachi T, Soriano S, Takeda M. Psychiatry Clin Neurosci. 65(2):183-90 2011 ( 1/2010 - 8/2011 )
    AIM: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia-like psychosis of epilepsy (SLPE). METHODS:   Twelve patients with SLPE and 14 non-psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four-factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM-induced activation of the DLPFC. RESULTS: We found that activation of the WM-compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non-psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. CONCLUSION: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought-processing in patients with SLPE.
  • Skerget K, Taler-Vercic A, Bavdek A, Hodnik V, Ceru S, Tusek-Znidaric M, Kumm T, Pitsi D, Pompe-Novak M, Palumaa P, Soriano S, Kopitar-Jerala N, Turk V, Anderluh G, Zerovnik E. Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells. J Biol Chem 285: 3201-10 2010 ( 1/2010 - 8/2011 )
    To contribute to the question of the putative role of cystatins in Alzheimer disease and in neuroprotection in general, we studied the interaction between human stefin B (cystatin B) and amyloid-beta-(1-40) peptide (Abeta). Using surface plasmon resonance and electrospray mass spectrometry we were able to show a direct interaction between the two proteins. As an interesting new fact, we show that stefin B binding to Abeta is oligomer specific. The dimers and tetramers of stefin B, which bind Abeta, are domain-swapped as judged from structural studies. Consistent with the binding results, the same oligomers of stefin B inhibit Abeta fibril formation. When expressed in cultured cells, stefin B co-localizes with Abeta intracellular inclusions. It also co-immunoprecipitates with the APP fragment containing the Abeta epitope. Thus, stefin B is another APP/Abeta-binding protein in vitro and likely in cells.
  • Engmann O, Hortobágyi T, Thompson AJ, Guadagno J, Troakes C, Soriano S, Al-Sarraj S, Kim Y, Giese KP. (2011). Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer''s disease. Biol Psychiatry 70:159-68. ( 7/2011 ) Link...
    BACKGROUND: The cyclin-dependent kinase 5 activator p35 can be cleaved into p25. Formation of p25 has been suggested to contribute to neurodegeneration in Alzheimer''s disease (AD). However, overexpression of low levels of p25 in mice enhances memory formation. Therefore, it has been suggested that p25 formation might be an event early in AD to compensate for impairments in synaptic plasticity. Ongoing p25 formation has been hypothesized to contribute to neurodegeneration at the later stages of AD. METHODS: Here, we tested the early compensation hypothesis by analyzing the levels of p25 and its precursor p35 in AD postmortem samples from different brain regions at different stages of tau pathology, using quantitative Western blots. Furthermore, we studied p35 and p25 during spatial memory formation. By employing quantitative mass spectrometry, we identified proteins downstream of p25, which were then studied in AD samples. RESULTS: We found that p25 is generated during spatial memory formation. Furthermore, we demonstrate that overexpression of p25 in the physiological range increases the expression of two proteins implicated in spine formation, septin 7 and optic atrophy 1. We show that the expression of p35 and p25 is reduced as an early event in AD. Moreover, expression of the p25-regulated protein optic atrophy 1 was reduced in a time course similar to p25 expression. CONCLUSIONS: Our findings suggest that p25 generation is a mechanism underlying hippocampal memory formation that is impaired in the early stages of AD. Our findings argue against the previously raised early compensation hypothesis and they propose that p25-mediated neurotoxicity does not occur in AD.
  • Nunes A, Pressey SN, Cooper JD, Soriano S. (2011). Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis. 42:349-59 ( 6/2011 )
    Niemann-Pick type C disease (NPC) is a lysosomal storage disorder which, at the cellular level, shows amyloid Aβ and tau pathologies comparable to those seen in the AD brain. Here, we have investigated, in a mouse model of NPC, the impact of removing the source of Aβ, namely APP, on the disease phenotype and on the expression levels and phosphorylation patterns of tau. We reasoned that removing APP from the NPC brain might help to unveil its impact on the disease phenotype and shed light on the mechanisms governing the interaction, both physiological and pathological, between APP function and tau homeostasis, at least in NPC. We show that, unexpectedly, loss of APP in NPC mice leads to poorer neuromuscular coordination and cumulative survival rates; exacerbation of their cholesterol abnormalities; higher levels of astrocytosis and dysregulation of tau homeostasis. Our results are consistent with a mechanism of neurodegeneration in the NPC and AD brains in which cholesterol dysregulation is a key early pathogenic event affecting tau homeostasis in parallel with, and independently of, amyloid accumulation.
  Scholarly Journals--Accepted
  • Castello MA, Soriano S. Rational heterodoxy: Cholesterol reformation of the amyloid doctrine (2013) 282-288  ( 1/2013 ) Link...
    According to the amyloid cascade hypothesis, accumulation of the amyloid peptide Aβ, derived by proteolytic processing from the amyloid precursor protein (APP), is the key pathogenic trigger in Alzheimer''''s disease (AD). This view has led researchers for more than two decades and continues to be the most influential model of neurodegeneration. Nevertheless, close scrutiny of the current evidence does not support a central pathogenic role for Aβ in late-onset AD. Furthermore, the amyloid cascade hypothesis lacks a theoretical foundation from which the physiological generation of Aβ can be understood, and therapeutic approaches based on its premises have failed. We present an alternative model of neurodegeneration, in which sustained cholesterol-associated neuronal distress is the most likely pathogenic trigger in late-onset AD, directly causing oxidative stress, inflammation and tau hyperphosphorylation. In this scenario, Aβ generation is part of an APP-driven adaptive response to the initial cholesterol distress, and its accumulation is neither central to, nor a requirement for, the initiation of the disease. Our model provides a theoretical framework that places APP as a regulator of cholesterol homeostasis, accounts for the generation of Aβ in both healthy and demented brains, and provides suitable targets for therapeutic intervention.
  Books and Chapters
  • Currais A, Hortobagyi T, Soriano S. The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer''s disease. In Cell Cycle Regulators in Alzheimer''s Disease. Editor: Jaya Padmanabhan, University of South Florida. Publisher: Transworld Research Network. ISBN 978-81-7895-447-9 ( 1/2010 - 8/2011 )
    This book describes the collective the research work in the emerging field of neuronal apoptosis associated to dysregulation of the cell cycle, and  is intended for researchers in the field of neurodegeneration. Link to publisher''s site http://www.trnres.com