Optimization of techniques for the maximal detection and quantification of Alzheimer’s-related neuropathology with digital imaging

Cummings, Brian J.; Mason, Amy J.L; Kim, Ronald C.; Sheu, Phillip C.‐Y.; Anderson, Aileen J.

doi:10.1016/s0197-4580(01)00316-5

Cited by 41 publications

(24 citation statements)

References 33 publications

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“…Briefly, every eighth section (ϳ12 per brain) was immunostained using antibodies directed against (1) A␤ (71-5800 A␤, 1:300 dilution; Zymed Laboratories, San Francisco CA), (2) A␤ precursor protein C-terminal fragments (CTFs) (CT20, 1:16,000 dilution; Calbiochem, San Diego, CA), or (3) hyperphosphorylated tau (AT8, 1:1000 dilution; Pierce, Rockford, IL) using ABC Vector Elite and diaminobenzidine kits (Vector Laboratories, Burlingame, CA). Antigen unmasking treatment, consisting of 5 min rinse in 99% formic acid, was performed to enhance A␤ immunoreactivity (IR) (Cummings et al, 2002).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…First, levels of positive immunoreactivity for A␤ and CTF antibodies were determined by immunohistochemistry load technique (Cummings et al, 2002;Rosario et al, 2006b). Load values were determined from selected 420 ϫ 330 m fields of immunolabeled sections that were captured and digitized using a video capture system [black and white CCD camera coupled to an Olympus Optical (Tokyo, Japan) BX40 upright microscope].…”

Section: Quantification Of Immunohistochemistrymentioning

confidence: 99%

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Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice

Carroll¹,

Rosario²,

Chang³

et al. 2007

J. Neurosci.

319

271

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Estrogen depletion in postmenopausal women is a significant risk factor for the development of Alzheimer's disease (AD), and estrogen-based hormonetherapymayreducethisrisk.However,theeffectsofprogesteronebothaloneandincombinationwithestrogenonADneuropathology remain unknown. In this study, we used the triple transgenic mouse model of AD (3xTg-AD) to investigate the individual and combined effects of estrogen and progesterone on ␤-amyloid (A␤) accumulation, tau hyperphosphorylation, and hippocampal-dependent behavioral impairments. In gonadally intact female 3xTg-AD mice, AD-like neuropathology was apparent by 3 months of age and progressively increased through age 12 months, a time course that was paralleled by behavioral impairment. Ovariectomy-induced depletion of sex steroid hormones in adult female 3xTg-AD mice significantly increased A␤ accumulation and worsened memory performance. Treatment of ovariectomized 3xTg-AD mice with estrogen, but not progesterone, prevented these effects. When estrogen and progesterone were administered in combination, progesterone blocked the beneficial effect of estrogen on A␤accumulation but not on behavioral performance. Interestingly, progesterone significantly reduced tau hyperphosphorylation when administered both alone and in combination with estrogen. These results demonstrate that estrogen and progesterone independently and interactively regulate AD-like neuropathology and suggest that an optimized hormone therapy may be useful in reducing the risk of AD in postmenopausal women.

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Section: Immunohistochemistrymentioning

confidence: 99%

Section: Quantification Of Immunohistochemistrymentioning

confidence: 99%

Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice

Carroll¹,

Rosario²,

Chang³

et al. 2007

J. Neurosci.

319

271

View full text Add to dashboard Cite

show abstract

“…nent but intracellular A␤ immunoreactivity is little (Iwatsubo et al, 1994;Cummings et al, 2002); (ii) in contrast to the Cterminus of A␤42, the N-terminus of intracellular A␤ is difficult to be detected by immunostaining (Chui et al, 2001;Mori et al, 2002); (iii) intraneuronal A␤ immunoreactivity might thus be due to cross-reaction of anti-A␤ antibodies with intraneuronal amyloid ␤-protein precursor (APP). However, similarly to the microwave protocol employed by D' Andrea et al (2003), we demonstrated that a heating protocol, i.e., hydrated autoclaving procedure, markedly enhanced intraneuronal A␤ immunoreactivity (Ohyagi et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Intraneuronal amyloid β42 enhanced by heating but counteracted by formic acid

Ohyagi

Tsuruta

Motomura

et al. 2007

Journal of Neuroscience Methods

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“…Immunoreactive load was calculated as percentage of total pixel area positively labeled, as previously described [20]. Mean load values were averaged from two to three nonoverlapping fields from each brain region in five sections per animal.…”

Section: Immunohistochemistrymentioning

confidence: 99%

P4‐006: Sex‐specific Effects of a High Fat Diet on Indices of Metabolic Syndrome in 3xTgAD Mice: Implications for Alzheimer's Disease

Barron

Rosario

Brown

et al. 2010

Alzheimer's & Dementia

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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 neuropathology in animal models. However, sex interacts with the metabolic outcomes of high fat diet and, therefore, may alter neuropathological consequences of dietary manipulations. This study examines the effects of sex and high fat diet on metabolic and AD-related neuropathological outcomes in 3xTg-AD mice. Three month-old male and female 3xTg-AD mice were fed either standard or high fat diets for 4 months. Obesity was observed in all high fat fed mice; however, ectopic fat accumulation, hyperglycemia and hyperinsulinemia were observed only in males. Interestingly, despite the different metabolic outcomes of high fat diet, the neuropathological consequences were similar: both male and female mice maintained under high fat diet exhibited significant worsening in behavioral performance and hippocampal accumulation of b-amyloid protein. Because high fat diet resulted in obesity and increased AD-like pathology in both sexes, these data support a role of obesity-related factors in promoting AD pathogenesis.

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Optimization of techniques for the maximal detection and quantification of Alzheimer’s-related neuropathology with digital imaging

Cited by 41 publications

References 33 publications

Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice

Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice

Intraneuronal amyloid β42 enhanced by heating but counteracted by formic acid

P4‐006: Sex‐specific Effects of a High Fat Diet on Indices of Metabolic Syndrome in 3xTgAD Mice: Implications for Alzheimer's Disease

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