Fimbria-fornix lesion does not affect APP levels and amyloid deposition in the hippocampus of APP+PS1 double transgenic mice

The deposition of amyloid beta peptides (Abeta) and cholinergic dysfunction are two characteristic features of Alzheimer's disease. Several studies have suggested that a compromised cholinergic transmission can increase the amount of amyloid precursor protein (APP) in the denervated cortex (or hippocampus); however, whether this will increase Abeta production is unknown. To investigate the relation between cholinergic neurotransmission and APP metabolism, and the possible role of cholinergic dysfunction in the development of amyloid neuropathology, we lesioned the fimbria-fornix pathway in APP+PS1 double transgenic mice, at 5 and 7 months of age. Three months and 11 months postlesion, the mice were sacrificed for biochemical and histopathological analyses. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus at both time points. Three months postlesion, hippocampal APP and Abeta levels were not significantly changed. At 11 months postlesion, the fimbria-fornix lesion did not result in an alteration in either the hippocampal Abeta levels or the extent of Abeta deposition, as assessed by amyloid plaque counts and image analysis of Abeta load in the 18-month-old APP+PS1 mice. Our findings indicate that APP metabolism in mice may be dissociated from cholinergic neurotransmission rather than related as previously suggested in other mammalian species.     

Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation

We investigated the effects of ovariectomy (OVX) and 17 beta-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (A beta) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the A beta-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to A beta-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of A beta or formation of amyloid plaques.     

Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology

The extracellular deposition of amyloid (A) peptides in plaques, and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). Plaques are surrounded by activated astrocytes and microglia, to study the relation between amyloid neuropathology and inflammation, we examined the changes in amyloid pathology in the hippocampus following three different treatments aimed at reducing the amyloid burden. (1) To investigate the effects of long-term cholinergic deafferentation, we lesioned the fimbria-fornix pathway in our AD-model mice at 7 months of age, and 11 months post-lesion the mice were sacrificed for histopathological analysis. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus, but the lesion did not result in an alteration in hippocampal A deposition and inflammation (i.e., numbers or staining density of astrocytes and microglia). (2) To investigate the effects of estrogen, we ovariectomized mice and treated them with estrogen (sham-lesion, zero dose, low dose, and high dose) and studied the pathology at different postsurgery intervals. Estrogen depletion (i.e., ovariectomy) or estrogen replacement did not affect A deposition or inflammation at any time point. (3) In the final studies, we treated mice with flurbiprofen and an NO-donating derivative of flurbiprofen (HCT 1026) for several months (from 6 till 14 months of age), and studied the A pathology and inflammation in the brain. Sham treatment, flurbiprofen, and the low-dose HCT 1026 did not affect pathology; however, a higher dose of HCT 1026 reduced both A load and amount of microglial activation surrounding plaques.     

阿尔茨海默病转基因动物模型的学习记忆能力改变及病理学观察

目的观察APPswe/PS1ΔE9双转基因小鼠的学习记忆功能及其病理学改变。方法 9月龄雄性APPswe/PS1ΔE9双转基因小鼠和9月龄雄性C57BL/6J小鼠各10只,采用Morris水迷宫检测各组小鼠学习记忆能力情况,并于水迷宫后灌注处死各组小鼠,采用改良Bielschowsky银染法以及尼氏染色法观察小鼠大脑组织病理学变化。结果水迷宫定位航行实验结果显示,APPswe/PS1ΔE9双转基因小鼠的逃避潜伏期与C57对照组小鼠相比明显延长(P<0.05);空间探索实验结果显示,APPswe/PS1ΔE9双转基因小鼠与C57对照组小鼠相比跨台次数减少(P<0.05)。改良Bielschowsky银染法结果显示,C57对照组小鼠大脑皮质未见明显改变,神经原纤维排列有序、稀疏。APPswe/PS1ΔE9双转基因小鼠大脑皮质神经原纤维肿胀,密集成宽带状,可见神经纤维缠结,有老年斑散在分布。尼氏染色结果显示,C57对照组小鼠海马各区神经细胞排列密集、整齐,胞浆中尼氏体丰富,大脑皮质尼氏小体呈深蓝色,细胞核淡蓝色,背景略呈浅蓝色;APPswe/PS1ΔE9双转基因小鼠神经元水肿,细胞数量减少,排列稀疏,细胞间隙增大,胞浆内尼氏体减少,分界不清,染成淡蓝色。结论 APPswe/PS1ΔE9双转基因AD小鼠能够较好的模拟AD患者的表现及病理过程,提供有效的实验动物模型。     

Synaptotrophic effects of human amyloid β protein precursors in the cortex of transgenic mice

The amyloid precursor protein (APP) is involved in Alzheimer's disease (AD) because its degradation products accumulate abnormally in AD brains and APP mutations are associated with early onset AD. However, its role in health and disease appears to be complex, with different APP derivatives showing either neurotoxic or neurotrophic effects in vitro. To elucidate the effects APP has on the brain in vivo, cDNAs encoding different forms of human APP (hAPP) were placed downstream of the neuron-specific enolase (NSE) promoter. In multiple lines of NSE-hAPP transgenic mice neuronal overexpression of hAPP was accompanied by an increase in the number of synaptophysin immunoreactive (SYN-IR) presynaptic terminals and in the expression of the growth-associated marker GAP-43. In lines expressing moderate levels of hAPP751 or hAPP695, this effect was more prominent in homozygous than in heterozygous transgenic mice. In contrast, a line with several-fold higher levels of hAPP695 expression showed less increase in SYN-IR presynaptic terminals per amount of hAPP expressed than the lower expressor lines and a decrease in synaptotrophic effects in homozygous compared with heterozygous offspring. Transgenic mice (2–24 months of age) showed no evidence for amyloid deposits or neurodegeneration. These findings suggest that APP may be important for the formation/maintenance of synapses in vivo and that its synaptotrophic effects may be critically dependent on the expression levels of different APP isoforms. Alterations in APP expression, processing or function could contribute to the synaptic pathology seen in AD.     

Longitudinal observation on CSF Abeta42 levels in young to middle-aged amyloid precursor protein/presenilin-1 doubly transgenic mice

To relate levels of beta-amyloid42 (Abeta42) in the cerebrospinal fluid (CSF) and brain in early Alzheimer's disease, we repeatedly measured CSF Abeta42 levels in transgenic mice carrying Swedish amyloid precursor protein and presenilin-1 mutations, at ages before and after amyloid deposition. Hippocampal Abeta42 levels were measured at the endpoints. In APPswe/PS1(A246E) mice, CSF Abeta42 levels significantly increased between 5 and 7 months of age but did not change between 8 and 13 months despite a rapid increase in brain Abeta42. Furthermore, a decline in CSF Abeta42 levels was observed between 6 and 9 months in APPswe/PS1dE9 mice with faster pathology. Interestingly, the initial CSF Abeta42 concentrations correlated more strongly with brain Abeta42 levels than the endpoint CSF Abeta42. Our results suggest that the levels of CSF Abeta42 initially reflect the rate of Abeta42 production, but after reaching a critical concentration stay in equilibrium, until plaque formation leads to decreased CSF Abeta42 levels.     

丙戊酸钠对APP/PS1双重转基因AD模型小鼠脑内老年斑和神经元的影响

目的 探讨丙戊酸钠 (valproic acid sodium salt,VPA)处理对淀粉样蛋白前体蛋白(β-amyloid precursor protein,APP)/早老素1(presenilin1,PS1)双重转基因阿尔茨海默病(Alzheimer's disease,AD)模型小鼠是否发挥神经保护作用.方法 对APP/PS1双重转基因AD模型种鼠交配后产下的子代进行基因分型,运用VPA 30 mg/(kg·d)和等量生理盐水腹腔注射APP/PS1双重转基因小鼠4周.药物处理后采用免疫组化、甲硫素S染色检测VPA对老年斑(senile plapues,SP)的影响,用Nissl染色、Tunel染色观察脑内神经元的变化,并采用ELISA定量检测小鼠脑内β-淀粉样蛋白(amyloid β peptide,Aβ)水平.结果 免疫组化及甲硫素S染色结果显示:VPA治疗组较生理盐水组的小鼠大脑皮质及海马区域的老年斑数量明显减少(t ＝ 7.78,P ＜ 0.01).Nissl染色发现VPA治疗组小鼠皮质及海马内的神经元数目较生理盐水组增加;Tunel染色显示VPA治疗组小鼠脑内凋亡神经元明显减少(t ＝ 5.95,P ＜ 0.01);ELISA结果提示VPA治疗组小鼠脑内Aβ40(t ＝ 4.23,P ＜ 0.01)和Aβ42(t ＝ 7.51,P ＜ 0.01)水平显著低于对照组.结论 VPA处理能显著减少AD模型小鼠减少脑内Aβ的沉积和老年斑的形成,通过减少神经元的凋亡来增加神经元的数量.     

Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice

Several novel transgenic mouse models expressing different mutant APPs in combination with mutant PS1 have been developed. These models have been analyzed to investigate the formation and progressive alterations of dystrophic neurites (DNs) in relation to Abeta deposits. In the most aggressive model, Abeta deposits appear as early as 2.5 months of age. Maturation of DNs was qualitatively quite similar among models and in some respect reminiscent of human AD pathology. From the onset of deposition, most if not all Abeta deposits were decorated with a high number of APP-, ubiquitin-, and MnSOD-immunoreactive DNs. Phosphorylated Tau DNs, however, appeared at a much slower rate and were more restricted. Mitochondrial dysfunction markers were observed in DNs: the frequency and the density per deposit of DNs accumulating cytochrome c, cytochrome oxidase 1, and Bax progressively increased with age. Later, the burden of reactive DNs was reduced around large compact/mature deposits. In addition, the previously described phenomenon of early intraneuronal Abeta accumulation in our models was associated with altered expression of APP protein as well as oxidative and mitochondrial stress markers occasionally in individual neurons. The present study demonstrates that oxidative and mitochondrial stress factors are present at several phases of Abeta pathology progression, confirming the neuronal dysfunction in APP transgenic mice.     

Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice

Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.     

X11α haploinsufficiency enhances Aβ amyloid deposition in Alzheimer's disease transgenic mice

The neuronal adaptor protein X11α/mint-1/APBA-1 binds to the cytoplasmic domain of the amyloid precursor protein (APP) to modulate its trafficking and metabolism. We investigated the consequences of reducing X11α in a mouse model of Alzheimer's disease (AD). We crossed hAPPswe/PS-1ΔE9 transgenic (AD tg) mice with X11α heterozygous knockout mice in which X11α expression is reduced by approximately 50%. The APP C-terminal fragments C99 and C83, as well as soluble Aβ40 and Aβ42, were increased significantly in brain of X11α haploinsufficient mice. Aβ/amyloid plaque burden also increased significantly in the hippocampus and cortex of one year old AD tg/X11α (+/−) mice compared to AD tg mice. In contrast, the levels of sAPPα and sAPPβ were not altered significantly in AD tg/X11α (+/−) mice. The increased neuropathological indices of AD in mice expressing reduced X11α suggest a normal suppressor role for X11α on CNS Aβ/amyloid deposition.     

Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes

This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP(670,671)) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein beta-amyloid (Abeta) neuropathology in APP+PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP+PS1 transgenic mice and their progressive Abeta deposition/neuroinflammation, Abeta neuropathology could be involved in these progressive cognitive impairments. As such, the APP+PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Abeta deposition/neuroinflammation.     

Lysosomal generation of amyloid β protein species in transgenic mice

Soluble amyloid β protein (Aβ)1–40 and highly amyloidogenic Aβ1–42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the Aβ precursor. Aβ1–42/43 and long Aβ species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with Aβ fibrils. These findings indicated that Aβ1–40, Aβ1–42, Aβ1–43 and longer Aβ species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate γ-secretase, leads to acceleration of Aβ amyloid formation.     

小檗碱对三转基因阿尔茨海默病小鼠的学习记忆和海马PSD95突触相关蛋白表达水平的影响

目的 探讨小檗碱(BBR)对三转基因阿尔茨海默病(AD)小鼠的学习记忆及海马组织PSD95突触蛋白表达水平的影响。方法 将30只三转基因(APP/Tau/PS1)AD小鼠按随机数字表法分成3组,即AD对照组、AD+25 mgBBR组、AD+50 mgBBR,每组各10只,后2组以灌胃方式且剂量分别为25 mg·kg^-1·d^-1、50 mg·kg^-1·d^-1,对照组给予等剂量生理盐水连续3个月灌胃处理; 采用Morris水迷宫方法探测各组AD小鼠行为学改变、空间记忆及探索情况; 免疫荧光染色检测各组小鼠海马组织突触后致密蛋白95(PSD95)阳性表达水平; Western blotting(WB)法检测各组三转基因AD小鼠海马脑组织PSD95蛋白、磷酸化蛋白激酶B(p-Akt)和磷酸化雷帕霉素靶蛋白(p-mTOR)表达水平及微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)自噬水平。结果 AD+25 mgBBR组的逃避潜伏期的学习记忆能力、免疫荧光PSD95表达水平以及PSD995、LC3-Ⅱ、p-Akt、p-mTOR蛋白表达水平与AD对照组比较均有明显差异(P<0.05); AD+50 mgBBR组逃避潜伏期的学习记忆能力、免疫荧光PSD95表达水平以及LC3-Ⅱ、p-Akt、p-mTOR表达水平与AD对照组比较差异均更明显(P<0.05,P<0.01)。结论 应用50 mg小檗碱能较好改善三转基因AD小鼠的学习记忆、空间探索能力,其机制可能是通过增加自噬水平LC3-Ⅱ调控Akt/mTOR信号通路,增加突触蛋白PSD95的表达水平及突触数量,以改善AD相关临床症状。     

Nicotine modulates expression of amyloid precursor protein and amyloid precursor-like protein 2 in mouse brain and in SH-SY5Y neuroblastoma cells

Epidemiological studies indicate that tobacco smoking can be protective against neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The objective of the present study was to examine the changes in gene expression induced by chronic oral nicotine administration (100 mug/ml in 2% saccharin for 14 days), with special emphasis on amyloid precursor protein (APP) and its homologue, amyloid precursor-like protein 2 (APLP2), in different brain regions of C57BL/6 mice using a pathway-focused microarray. Our results revealed that nicotine stimulated mRNA expression of APP in the amygdala (64%; P = 0.003) and hippocampus (32%; P = 0.034) and of APLP2 in the amygdala (39%; P = 0.002). These results were verified by quantitative real-time RT-PCR except that expression of APLP2 was also significantly upregulated by nicotine in the hippocampus. In addition, in vitro nicotine treatment of SH-SY5Y neuroblastoma cells resulted in a significant increase in expression of APP protein, soluble APP, and APLP2, whereas co-treatment with mecamylamine (an antagonist of nicotinic acetylcholine receptors) attenuated the stimulating effect of nicotine on APP and APLP2 expression. These findings suggest that nicotine treatment facilitates the increase in the expression of mRNA and protein of the APP and APLP2 genes in rat brain and SH-SY5Y neuroblastoma cells.     

Aged wild-type and APP, PS1, and APP + PS1 mice present similar deficits in associative learning and synaptic plasticity independent of amyloid load

Wild-type and single-transgenic (APP, PS1) and double-transgenic (APP + PS1) mice were studied at three different (3-, 12-, and 18-month-old) age periods. Transgenic mice had reflex eyelid responses like those of controls, but only 3-month-old mice were able to fully acquire conditioned eyeblinks, using a trace paradigm, whilst 12-month-old wild-type and transgenic mice presented intermediate values, and 18-month-old wild-type and transgenic mice were unable to acquire this type of associative learning. 18-month-old wild-type and transgenic mice presented a normal synaptic activation of CA1 pyramidal cells by the stimulation of Schaffer collaterals, but they did not show any activity-dependent potentiation of the CA3–CA1 synapse across conditioning sessions, as was shown by 3-month-old wild-type mice. Moreover, 18-month-old wild-type and transgenic mice presented a noticeable deficit in long-term potentiation evoked in vivo at the hippocampal CA3–CA1 synapse. The 18-month-old wild-type and transgenic mice also presented a significant deficit in prepulse inhibition as compared with 3-month-old controls. Except for results collected by prepulse inhibition, the above-mentioned deficits were not related with the presence of amyloid β deposits. Thus, learning and memory deficits observed in aged wild-type and transgenic mice are not directly related to the genetic manipulations or to the presence of amyloid plaques.     

The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice

The current study addresses the morphoregulatory effects of human amyloid precursor protein expression on neocortical pyramidal cells in vivo. For this purpose, a transgenic mouse line was used that expresses wild-type human amyloid precursor protein (APP) at levels similar to endogenous mouse APP. This strain does not develop Alzheimer's disease-related pathology which allowed to study effects of APP or APP cleavage products but excluded the influence of amyloid deposits. Commissural projecting pyramidal neurons of layers II/III within the primary somatosensory cortex were retrogradely labelled by injection of biotinylated dextran amine into the corpus callosum. In transgenic mice, computer-aided morphometric analysis revealed an increase in the surface area of proximal and intermediate basal dendritic segments resulting from an enlarged diameter. On the other hand, the length of the same segments was reduced. Both basal and apical dendrites were characterized by a higher dendritic density within the proximal and intermediate fields. Although the total spatial extension of basal and apical dendrites remained unchanged, a moderate withdrawal of arbors is suggested. The results implicate a physiological function for APP in regulatory mechanisms of neuronal morphogenesis.     

Plaque-associated α-synuclein (NACP) pathology in aged transgenic mice expressing amyloid precursor protein

Patients with the Lewy body variant (LBV) of Alzheimer's disease (AD) have ubiquitinated intraneuronal and neuritic accumulations of α-synuclein and show less neuron loss and tau pathology than other AD patients. Aged Tg2576 transgenic mice overexpressing human βAPP695. KM670/671NL have limited neuron loss and tau pathology, but frequent ubiquitin- and α-synuclein-positive, tau-negative neurites resembling those seen in the LBV of AD.     

Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined amyloid and tau-pathology

Describing and understanding the pathological processes which devastate the brain of Alzheimer's disease (AD) patients remains a major target for experimental biology. We approached this problem by generating different types of single and double transgenic mice that develop pathological hallmarks of AD. In APP-V717 mice, the progression from intracellular amyloid to diffuse and senile plaques with vascular deposits, is preceded by early defects in cognition and LTP. In Tau-P301L mice, the morbid tauopathy with intracellular filaments, cause mortality before age 1 year. Ageing APP-V717IxTau-P301L double tg mice (14-17 months) have combined AD-like pathology in hippocampus and cortex consisting of amyloid plaques and neurofibrillary tangles. Remarkably, while Tau-P301L mice die before age 1 year, the APP-V717IxTau-P301L double tg mice survive much longer, which correlates with alleviation of tauopathy in hindbrain, despite aggravation in forebrain. This hypothesis is corroborated in Tau-P301LxGSK-3B double transgenic mice, which have also an extended lifespan relative to Tau-P301L mice, that correlates with reduction of brainstem tauopathy. At the same time, Tau-P301LxGSK-3B mice have dramatic forebrain tauopathy, with "tangles in almost all neurons", although without hyper-phosphorylation of Tau. The data corroborate the hypothesis that GSK-3B is the missing link between the amyloid and tau-pathology, and position GSK-3B as prominent player in the pathogenesis in AD.     

Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains

Amyloid precursor protein (APP) is a ubiquitously expressed membrane spanning glycoprotein which is endoproteolytically processed to Aβ, a 39–43 amino acid peptide that is the main component of senile plaques in Alzheimer Disease (AD). APP is a member of a highly conserved gene family, including Amyloid Precursor-Like Proteins (APLPs) APLP1 and APLP2. We now characterize APLP1 and APLP2 mRNA and protein expression in AD and aged control brains. Using in situ hybridization in hippocampal tissue from control and AD brain, we show that APLP1 and APLP2 mRNA are expressed primarily in the granule cells of the dentate gyrus, in areas CA1–CA3, and subiculum. Immunohistochemistry reveals staining for both APLP1 and APLP2 in neurons and blood vessels in AD and control cases. In addition, in AD brain, large dystrophic neurites in a subset of senile plaques are conspicuously labeled with APLP1 and APLP2 antibodies. The aged control brains have significantly fewer immunoreactive plaques and dystrophic neurites. The regional, cellular, and subcellular distribution of APLP1 and APLP2 overlap with each other and with APP. These observations support the hypothesis that the members of this family of proteins may perform similar functions.     

Enhanced localization of amyloid β precursor protein in the rat hippocampus following long-term adrenalectomy

Using various antibodies to the amyloid ß precursor protein (APP) associated with Alzheimer's disease, we investigated changes in the distribution of APP in the hippocampus and neocortex of adrenalectomized (ADX) rats. In contrast to sham-operated controls, ADX rats euthanised after a survival period of 5 months showed striking APP reactivity in the CA1–CA4 fields and in the surviving cells in the dentate gyrus. Our results suggest the enhanced APP reactivity in hippocampal neurons may pertain to previous observations on the accumulation of APP fragments in the neocortex during ischemic or traumatic injury. Thus, long-term hormone deprivation would be another factor, which may influence the expression of APP in brain.