Christian J Pike

Christian J Pike
University of Southern California | USC · School of Gerontology

PhD

About

155
Publications
17,781
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16,459
Citations
Citations since 2016
36 Research Items
4648 Citations
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
Introduction
Skills and Expertise
Additional affiliations
January 1999 - present
January 1991 - December 1999
University of California, Irvine

Publications

Publications (155)
Article
Full-text available
The most significant genetic risk factor for developing late-onset Alzheimer's disease (AD) is the ε4 allele of apolipo-protein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD...
Article
Full-text available
Alzheimer's disease (AD) is characterized by numerous sexual dimorphisms that impact the development, progression, and likely the strategies to prevent and treat the most common form of dementia. In this review, we consider this topic from a female perspective with a specific focus on how women's vulnerability to the disease is affected by the indi...
Article
Full-text available
The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer’s disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term...
Preprint
Full-text available
The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E ( APOE4 ). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here we show astroglial interactions with amyloid plaques in the EFAD...
Article
Age-related testosterone depletion in men is a risk factor for Alzheimer's disease (AD). How testosterone modulates AD risk remains to be fully elucidated, although regulation of tau phosphorylation has been suggested as a contributing protective action. To investigate the relationship between testosterone and tau phosphorylation, we first evaluate...
Article
Full-text available
Two of the primary risk factors for late onset Alzheimer’s Disease (AD) are aging and APOE genotype. While the causal relationship between aging and AD is not well defined, there are strong leads from shared phenotypes such as decreased metabolic function and increased inflammation. APOE genotype may be linked to AD phenotypes through the regulatio...
Article
In this study, we investigate the hypothesis that recently identified longevity‐promoting intervention 17α‐estradiol (17αE2) will protect against senescent changes in brain and throughout the body that are associated with APOE4 and heightened AD risk. The most significant genetic factor for late‐onset Alzheimer’s disease (AD) is the apolipoprotein...
Article
Background: The predominant genetic risk factor for late-onset Alzheimer's disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE4-related risk of developing AD is modified by sex, with women showing greater risk than men. Regardless of APOE genotype, women exhibit a higher prevalence and lifetime risk of AD. Extensive human and animal mo...
Article
Full-text available
Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). APOE4 is known to affect the function of microglia, but to what extent this gene drives microglial gene expression has thus far not been examined. Using a transgenic mouse model of AD that expresses human APOE, we identify a unique transcriptional...
Article
Women have higher prevalence and risk for developing Alzheimer’s disease (AD) than men. The reason(s) underlying this sex difference in AD has not been definitively established but has been theorized to reflect sex‐specific patterns in age‐related depletion of sex steroid hormones, primarily the loss of estrogens in women. Not well considered is th...
Article
Relative length of the index (second digit; 2D) and ring (fourth digit; 4D) fingers on the right hand (2D:4D) is taken to indicate prenatal hormone levels. Lower 2D:4D (i.e., 4D relatively longer) represents more androgen exposure, with men showing lower 2D:4D on average than women. Women from opposite sex twin pairs have lower 2D:4D compared to wo...
Article
Alzheimer's disease is characterized by sex differences that may involve sex hormone exposure during development. Finger length ratios, an indirect measure of prenatal androgen exposure, were found to significantly differ in women with and without dementia. This finding links a relatively feminine in utero development with vulnerability to dementia...
Article
Full-text available
Introduction: Hormones may be one possible mechanism underlying sex differences in dementia incidence. We examined whether presumed differential prenatal hormone milieu is related to dementia risk by comparing dementia rates in same- and opposite-sex dizygotic twin pairs in male and female twins. Methods: The sample comprised 43,254 individuals...
Chapter
Studies of Alzheimer’s disease (AD) using experimental systems most often involve transgenic mouse models that are characterized by neural accumulation of β-amyloid protein (Aβ), which is widely hypothesized to have a key role in AD pathogenesis. Quantification of Aβ in transgenic mice typically is accomplished through both biochemical and histoche...
Article
Full-text available
Vulnerability to Alzheimer’s disease (AD) is increased by several risk factors, including midlife obesity, female sex, and the depletion of estrogens in women as a consequence of menopause. Conversely, estrogen-based hormone therapies have been linked with protection from age-related increases in adiposity and dementia risk, although treatment effi...
Article
Full-text available
Abstract Microglia affect Alzheimer’s disease (AD) pathogenesis in opposing manners, by protecting against amyloid accumulation in early phases of the disease and promoting neuropathology in advanced stages. Recent research has identified specific microglial interactions with amyloid plaques that exert important protective functions including atten...
Article
Development of Alzheimer's disease (AD) is regulated by interactive effects of genetic and environmental risk factors. The most significant genetic risk factor for AD is the ε4 allele of apolipoprotein E ( APOE4), which has been shown to exert greater AD risk in women. An important modifiable AD risk factor is obesity and its associated metabolic d...
Article
Full-text available
Background: Obesity exerts negative effects on brain health, including decreased neurogenesis, impaired learning and memory, and increased risk for Alzheimer's disease and related dementias. Because obesity promotes glial activation, chronic neuroinflammation, and neural injury, microglia are implicated in the deleterious effects of obesity. One p...
Article
Full-text available
Abstract Advanced age is associated with a decline in cognitive function, likely caused by a combination of modifiable and non-modifiable factors such as genetics and lifestyle choices. Mounting evidence suggests that humanin and other mitochondrial derived peptides play a role in several age-related conditions including neurodegenerative disease....
Article
Full-text available
Risk for Alzheimer's disease (AD) is affected by multiple factors, including aging, obesity, and low testosterone. We previously showed that obesity and low testosterone independently and interactively exacerbate AD-related outcomes in young adult rodents. The goals of the present study are two-fold: to examine whether the effects of an obesogenic...
Article
Full-text available
Alzheimer's disease (AD) pathogenesis is a multifactorial process that involves numerous pathways within the central nervous system. Thus, interventions that interact with several disease-related pathways may offer an increased opportunity for successful prevention and treatment of AD. Translocator protein 18 kD (TSPO) is a mitochondrial protein th...
Article
Full-text available
A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen “a toxic environmental poison” could be also indispensable for life (Beckman and Ames Physiol Rev 78...
Article
Full-text available
Alzheimer’s disease (AD) risk is modified by both genetic and environmental risk factors, which are believed to interact to cooperatively modify pathogenesis. Although numerous genetic and environmental risk factors for AD have been identified, relatively little is known about potential gene-environment interactions in regulating disease risk. The...
Article
Full-text available
Depletion of ovarian hormones at menopause is associated with increased Alzheimer’s disease (AD) risk. Hormone loss also increases central adiposity, which promotes AD development. One strategy to improve health outcomes in postmenopausal women is estrogen-based hormone therapy (HT), though its efficacy is controversial. The window of opportunity h...
Data
Phospho-tau immunoreactivity increases with age in female 3xTg-AD mice. Images show AT8 phospho-tau immunostaining from early middle-aged (MA) mice maintained on (A) normal and (C) high-fat diets. Increased numbers of AT8-immunreactive cells in late middle-ages mice under both dietary conditions (B, D). Scale bar measures 50 μm. (PDF)
Data
Immunoreactivity levels of Aβ but not C-terminal fragments (CTF) of amyloid precursor protein increase with age in 3xTg-AD females. (A-C) CTF immunoreactivity does not change with age. (D) A high magnification (100x) of CTF staining in subiculum shows immunoreactivity is largely in cell periphery and/or membranes of neurons. (E-G) Aβ staining incre...
Article
Full-text available
Men and women exhibit differences in the development and progression of Alzheimer's disease (AD). The factors underlying the sex differences in AD are not well understood. This Review emphasizes the contributions of sex steroid hormones to the relationship between sex and AD. In women, events that decrease lifetime exposure to estrogens are general...
Article
Full-text available
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder for which there are no effective strategies to prevent or slow its progression. Because AD is multifactorial, recent research has focused on understanding interactions among the numerous risk factors and mechanisms underlying the disease. One mechanism through which several risk...
Article
Full-text available
MOSER, V.A. and Pike, C.J. Obesity and sex differences in Alzheimer's disease. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, 2015.-Alzheimer's disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Int...
Article
Full-text available
The APOE4 allele confers greater risk of Alzheimer’s Disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that e...
Article
Full-text available
Citation: Christensen A and Pike CJ (2015) Menopause, obesity and inflammation: interactive risk factors for Alzheimer's disease. Front. Aging Neurosci. 7:130. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, the development of which is regulated by several environmental and genetic risk factors. Two factors theorized to con...
Article
The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological...
Article
Full-text available
Because the estrogen-based hormone therapy (HT) in postmenopausal women typically contains a progestogen component, understanding the interactions between estrogens and progestogens is critical for optimizing the potential neural benefits of HT. An important issue in this regard is the use of continuous versus discontinuous hormone treatments. Alth...
Article
Full-text available
Background Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer¿s disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices i...
Article
Full-text available
Obesity, metabolic syndrome, and type 2 diabetes (T2D) are related disorders with widespread deleterious effects throughout the body. One important target of damage is the brain. Persons with metabolic disorders are at significantly increased risk for cognitive decline and the development of vascular dementia and Alzheimer's disease. Our review of...
Article
Full-text available
The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed sele...
Article
Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we i...
Article
Full-text available
Multiple factors of metabolic syndrome have been implicated in the pathogenesis of Alzheimer's disease (AD), including abdominal obesity, insulin resistance, endocrine dysfunction and dyslipidemia. High fat diet, a common experimental model of obesity and metabolic syndrome, has been shown to accelerate cognitive decline and AD-related neuropatholo...
Article
Ligands of the translocator protein (TSPO) elicit pleiotropic neuroprotective effects that represent emerging treatment strategies for several neurodegenerative conditions. To investigate the potential of TSPO as a therapeutic target for Alzheimer's disease (AD), the current study assessed the effects of the TSPO ligand Ro5-4864 on the development...
Article
Full-text available
Multiple factors of metabolic syndrome have been implicated in the pathogenesis of Alzheimer's disease (AD), including abdominal obesity, insulin resistance, endocrine dysfunction and dyslipidemia. High fat diet, a common experimental model of obesity and metabolic syndrome, has been shown to accelerate cognitive decline and AD-related neuropatholo...
Article
Although neuroactive steroids exert neuroprotective actions in different experimental models of neurodegenerative diseases, including those of Alzheimer's disease (AD), their relationships with aged related physiologic and pathologic brain changes remain to be clarified. In this study the levels of pregnenolone, dehydroepiandrosterone, progesterone...
Article
Full-text available
The accumulation of β-amyloid protein (Aβ) is a key risk factor in the development of Alzheimer's disease. The ovarian sex steroid hormones 17β-estradiol (E(2)) and progesterone (P(4)) have been shown to regulate Aβ accumulation, although the underlying mechanism(s) remain to be fully elucidated. In this study, we investigate the effects of E(2) an...
Article
During normal aging, men experience a significant decline in testosterone levels and a compensatory elevation in levels of gonadotropin luteinizing hormone (LH). Both low testosterone and elevated LH have been identified as significant risk factors for the development of Alzheimer's disease (AD) in men. It is unclear whether changes in testosterone...
Article
Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) uses threshold cycles (Ct values) for measuring relative gene expression. Ct values are signal-to-noise data composed of target gene expression and multiple sources of confounding variations. Data analysis is to minimize technical noises, evaluate biological variances,...
Article
Age-related loss of sex steroid hormones is a established risk factor for the development of Alzheimer's disease (AD) in women and men. While the relationships between the sex steroid hormones and AD are not fully understood, findings from both human and experimental paradigms indicate that depletion of estrogens in women and androgens in men incre...
Article
Caspases, a family of cysteine proteases, are widely activated in neurons and glia in the injured brain, a response thought to induce apoptosis. However, caspase activation in astrocytes following injury is not strongly associated with apoptosis. The present study investigates the potential role of caspase activation in astrocytes with another char...
Article
Full-text available
This study investigated the impact of chronic exposure to continuous (CoP4) versus cyclic progesterone (CyP4) alone or in combination with 17β-estradiol (E2) on gene expression profiles targeting bioenergetics, metabolism and inflammation in the adult female rat hippocampus. High-throughput qRT-PCR analyses revealed that ovarian hormonal depletion...
Data
Gene expression changes in response to different hormone interventions and treatment paradigms. (DOCX)
Data
Taqman gene expression assays. (DOCX)
Data
Gene expression Ct values. (XLS)
Article
Full-text available
A promising strategy to delay and perhaps prevent Alzheimer's disease (AD) is to identify the age-related changes that put the brain at risk for the disease. A significant normal age change known to result in tissue-specific dysfunction is the depletion of sex hormones. In women, menopause results in a relatively rapid loss of estradiol and progest...
Article
Normal, age-related depletion of the androgen testosterone is a risk factor for Alzheimer's disease (AD) in men. Previously, we reported that experimental androgen depletion significantly accelerates development of AD-like neuropathology in the 3xTg-AD triple-transgenic mouse model of AD, an effect prevented by androgen treatment. Because testoster...
Article
The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly g...
Article
J. Neurochem. (2010) 115, 1277–1287. While both 17β-estradiol (E2) and progesterone (P4) are neuroprotective in several experimental paradigms, P4 also counteracts E2 neuroprotective effects. We recently reported that a 4-h treatment of cultured hippocampal slices with P4 following a prolonged (20 h) treatment with E2 eliminated estrogenic neuropro...
Article
Androgens can protect neurones from injury, although androgen neuroprotection is not well characterised in terms of either specificity or mechanism. In the present study, we compared the ability of androgens to protect neurones against a panel of insults, empirically determined to induce cell death by apoptotic or non-apoptotic mechanisms. Three cr...