APP/PS1双转基因小鼠早期记忆功能障碍与胆碱能系统的关系研究

目的观察转APP/PS1基因阿尔茨海默病小鼠(APP/PS1小鼠)早期空间学习记忆功能及乙酰胆碱能系统的变化以及两者之间的相关性,探讨阿尔茨海默病早期学习记忆障碍的发病机制。方法应用Morris水迷宫法评定3月龄APP/PS1小鼠及相应野生型(WT)小鼠的空间学习记忆功能;采用免疫组织化学及组织化学染色方法检测脑组织中β-淀粉样蛋白(Aβ)斑块沉积情况;采用ELISA法检测脑组织中乙酰胆碱(ACh)含量以及胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AChE)活性,并探讨小鼠脑组织中ACh含量与其空间记忆能力、ChAT活性的相关性。结果水迷宫评定结果显示两组小鼠到达平台的潜伏期无统计学差异(P>0.05);APP/PS1小鼠在目标象限的游泳时间百分比〔(29.02±4.27)%〕和距离百分比〔(28.85±3.77)%〕较WT小鼠均下降(P<0.05)。APP/PS1小鼠脑组织中尚无Aβ斑块的沉积。APP/PS1小鼠脑组织中ACh含量〔(45.23±1.40)ng/g prot〕和ChAT活性〔(279.53±12.13)U/g组织湿重〕均较WT小鼠〔分别为(54.08±4.84)ng/gprot、(315.84±11.32)U/g组织湿重〕显著降低(P<0.05),两组小鼠脑组织中AChE活性无统计学差异(P>0.05)。小鼠脑组织中ACh含量与其空间记忆功能(目标象限航行时间百分比、目标象限航行路程百分比)呈正相关(r=0.861、r=0.874,P<0.05),ACh含量与ChAT活性呈正相关(r=0.926,P<0.05)。结论 APP/PS1小鼠空间记忆功能障碍、ACh含量减少和ChAT活性降低可发生于Aβ斑块沉积之前。脑组织中ACh含量减少和ChAT活性降低可能与APP/PS1小鼠记忆功能损害密切相关。     

阿尔茨海默病APPswe/PS1dE9双转基因型与野生型小鼠学习记忆能力的比较

目的：比较不同年龄段阿尔茨海默病（AD）APPswe/PS1dE9双转基因型与野生型小鼠的学习记忆能力。方法：C57BL/6J雌鼠与C3H/HeJ雄鼠交配产下F1代,再将F1代与3月龄的APPswe/PS1dE9双转基因型小鼠交配产下F2代。提取F2代小鼠鼠尾DNA,PCR扩增目的基因并鉴定。依据是否含APP和PS1基因分为转基因型组和野生型对照组,小鼠分别于6、8月龄行Morris水迷宫实验,11月龄行Y迷宫实验检测学习记忆能力。结果：繁育F2代小鼠33只,其中转基因型组18只,野生型对照组15只。6月龄转基因型与野生型小鼠定位航行实验潜伏期的差异无统计学意义,空间探索实验目标象限时间和路程百分比的差异无统计学意义（P〉0.05）。与8月龄野生型小鼠比较,转基因型小鼠定位航行实验第1天潜伏期延长（P〈0.05）。与11月龄野生型小鼠比较,转基因型小鼠达到学会标准的训练次数增加（P〈0.05）。结论：ADAPPswe/PS1dE9双转基因型与野生型小鼠比较,于11月龄时出现学习记忆能力障碍。     

姜黄素对APP/PS1双转基因小鼠认知功能、炎症反应及海马区突触素表达的影响

目的 探讨姜黄素对APP/PS1双转基因小鼠认知功能、炎症反应及海马区突触素表达的影响。方法 60只6月龄APP/PS1双转基因雄性小鼠随机分为A组、B组和C组,各20只;A组采用姜黄素100mg/kg/d加入小鼠饲料喂养,B组采用姜黄素300mg/kg/d喂养,C组采用姜黄素600mg/kg/d喂养;3组均喂养6个月。治疗前、治疗3、6个月,采用Morris水迷宫实验评估小鼠认知功能,采用免疫吸附试验法检测尾静脉血血清白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）等炎症因子水平;治疗6个月,采用免疫组化染色法检测小鼠海马 CA1 区突触素表达情况。结果 姜黄素治疗3、6个月,3组小鼠认知功能明显改善（P<0.05）,血清IL-6、TNF-α水平明显降低（P<0.05）。与A组比较,B组和C组治疗3、6个月认知功能明显改善（P<0.05）,血清IL-6、TNF-α水平均明显降低（P<0.05）,海马CA1区突触素表达水平明显升高（P<0.05）。而B组与C组均无统计学差异（P>0.05）。结论 姜黄素有助于改善APP/PS1双转基因小鼠海马突触素表达,抑制小鼠炎症反应,改善小鼠认知功能。     

阿尔茨海默病APPswe/PS1dE9双转基因小鼠的病理生化和行为学研究(英文)

目的阿尔茨海默病(Alzheimer’sdisease,AD)APPswe/PS1dE9双转基因小鼠已被广泛运用于各种实验研究。AD小鼠脑内产生过量的β淀粉样蛋白(Aβ),后者会影响突触功能和中枢神经系统的发育。然而,该转基因小鼠模型的生化和行为学特征却未见报道。本研究旨在对该小鼠模型的病理从生化和行为学角度进行检测。方法对6月和12月龄转基因和野生型小鼠取血约100μL,1200g离心后,分离血清。在小鼠6月和12月龄时,进行为期15天的辐射状六臂水迷宫实验。ELISA法检测血清和大脑中Aβ1-40和Aβ1-42的含量,以及血清中8-羟基脱氧鸟苷的含量。比较转基因和野生型小鼠大脑不同部位中α-,β-和γ-分泌酶活性的差异。结果在6月龄之前,APP-swe/PS1dE9双转基因小鼠的死亡率约为35%,这些死亡的小鼠脑内Aβ1-40和Aβ1-42水平较高,两者比例约为1:10。在6月和12月龄时,转基因小鼠血清中Aβ1-40水平均显著高于Aβ1-42水平,Aβ1-40与Aβ1-42比例为2.37:1。在12月龄时,转基因小鼠大脑中Aβ1-42水平显著高于Aβ1-40水平,两者比例约为2.17:1,并且在不同脑区中,Aβ1-42和Aβ1-40含量变化较大。在小脑、前、后部皮质层以及海马中,Aβ1-42水平显著高于Aβ1-40。分泌酶活性在转基因和野生型小鼠之间以及在不同脑部位之间没有很大的差异,这提示PS1转基因并没有导致高γ-分泌酶活性,该基因可能使γ-分泌酶更有效的切割和产生Aβ1-42。此外,转基因小鼠血清中8-羟基脱氧鸟苷含量较野生型小鼠升高,但没有显著性差异。行为学结果显示,在6月龄时,转基因小鼠与野生型相比呈现出显著的记忆障碍,到12月龄时,这种障碍变得更为严重,表现为水迷宫实验中产生更多的错误。结论 APPswe/PS1dE9双转基因小鼠最早在6月龄时就能很好地模拟早发性AD,可用于实验研究。     

SOD1-G93A转基因小鼠的鉴定方法比较

目的建立一种简便、节省和准确的肌萎缩侧索硬化(ALS)hSOD1-G93A转基因小鼠DNA提取及基因鉴定方法。方法以B6SJL-BTg(SOD1-G93A)1Gur/J半合子雄鼠与B6SJLF1雌鼠交配产仔,剪尾尖约1mm,提取组织DNA,PCR扩增hSOD1基因片断,电泳后观察结果并对PCR产物进行纯化、测序及BLAST验证。同时留取鼠尾血50～100μl,提取血DNA并PCR扩增作为对照,比较两者之间的符合率。结果hSOD1-G93A阳性鼠约占54%,基本符合孟德尔遗传规律。鼠尾组织及血DNA鉴定结果符合率为100%。结论鼠尾尖组织DNA提取及鉴定是一种简便易行、节省经费并且准确可靠的方法。     

阿尔茨海默病APPswe/PS1dE9双转基因小鼠的病理生化和行为学研究(英文)

目的阿尔茨海默病(Alzheimer’sdisease,AD)APPswe/PS1dE9双转基因小鼠已被广泛运用于各种实验研究。AD小鼠脑内产生过量的β淀粉样蛋白(Aβ),后者会影响突触功能和中枢神经系统的发育。然而,该转基因小鼠模型的生化和行为学特征却未见报道。本研究旨在对该小鼠模型的病理从生化和行为学角度进行检测。方法对6月和12月龄转基因和野生型小鼠取血约100μL,1200g离心后,分离血清。在小鼠6月和12月龄时,进行为期15天的辐射状六臂水迷宫实验。ELISA法检测血清和大脑中Aβ1-40和Aβ1-42的含量,以及血清中8-羟基脱氧鸟苷的含量。比较转基因和野生型小鼠大脑不同部位中α-,β-和γ-分泌酶活性的差异。结果在6月龄之前,APP-swe/PS1dE9双转基因小鼠的死亡率约为35%,这些死亡的小鼠脑内Aβ1-40和Aβ1-42水平较高,两者比例约为1:10。在6月和12月龄时,转基因小鼠血清中Aβ1-40水平均显著高于Aβ1-42水平,Aβ1-40与Aβ1-42比例为2.37:1。在12月龄时,转基因小鼠大脑中Aβ1-42水平显著高于Aβ1-40水平,两者比例约为2.17:1,并且在不同脑区...     

APP/PS1转基因AD模型小鼠海马自噬及相关信号通路研究

目的 研究β-淀粉样前体蛋白/早老素1(amyloid precursor protein/presenilin 1,APP/PS1)双转基因阿尔茨海默病(Alzheimer disease,AD)模型小鼠不同年龄阶段自噬水平变化,及蛋白激酶B(protein kinase B,Akt)/哺乳动物雷帕霉素靶蛋白(mam...     

加兰他敏对APP/PS1转基因小鼠海马区星形胶质细活化及C/EBPβ表达的影响

目的研究加兰他敏对APP/PS1转基因小鼠海马区星形胶质细胞活化、C/EBPβ表达及行为学的影响。方法选取10月龄雄性APP/PS1转基因小鼠20只,随机分为模型对照组(10只)和治疗组(10只),同月龄、同背景的C57BL/6野生型雄性小鼠10只作为正常对照组。治疗组皮下注射加兰他敏溶液5mg/kg,2次/d,连续治疗8周,正常对照组和模型对照组给予皮下注射等量生理盐水。应用Morris水迷宫实验于干预治疗8周后开始测定各组小鼠空间学习记忆能力,连续7d,采用免疫组织化学、免疫荧光及Western-blot方法观察各组小鼠海马区星形胶质细胞活化及C/EBPβ表达水平。结果与正常对照组相比,模型对照组和治疗组小鼠Morris检测第5、6天平均逃避潜伏期延长,穿越平台次数减少(P0.05,P0.05),而治疗组其逃避潜伏期较模型对照组缩短(P0.05),穿越平台次数增多(P0.05);同时治疗组小鼠星形胶质细胞活化被明显抑制,胶质纤维酸性蛋白(GFAP)的阳性表达面积〔(5.003±0.823)%〕及C/EBPβ的表达量(87.711±14.622)较模型对照组〔(7.116±1.040)%,119.920±16.901〕明显减少(P0.05,P0.05)。结论加兰他敏改善APP/PS1转基因AD小鼠的学习记忆能力可能与其抑制星形胶质细胞的活化及C/EBPβ的表达有关。     

APP17肽对APP转基因小鼠学习记忆能力和海马神经细胞凋亡的影响

目的观察APP(-βamyloid precursop protein,APP)17肽(APP695中319-335肽段)对APP转基因小鼠(APP695V717I)学习、记忆能力及海马神经细胞凋亡的影响。方法3月龄的APP695转基因小鼠随机分为模型组和APP17肽治疗组,正常对照组采用月龄和性别与之相匹配的C57BL/6J小鼠。APP17肽治疗组给予皮下注射APP17肽,每只每次0.34μg,每周3次;模型组和正常对照组给予等体积NS。应用水迷宫试验观察小鼠学习、记忆功能的变化,以流式细胞技术分析海马神经细胞凋亡率和线粒体膜电位的变化。结果(1)水迷宫试验结果显示,模型组小鼠存在明显学习和记忆功能障碍,其第3、4、5天游完全程的时间[(93.22±16.35)、(86.73±20.26)、(77.13±29.35)s]和错误反应次数[(6.63±2.16)、(5.81±2.13)、(5.33±1.41)次]均较正常对照组[分别为(70.89±20.19)、(61.25±21.88)、(54.63±16.92)s和(5.01±1.93)、(2.97±0.96)、(2.31±1.01)次]增多(P<0.05);APP17肽治疗组小鼠的行为学障碍明显轻于模型组(P<0.05),其上述水迷宫检测结果与正常对照组比较差异无统计学意义。(2)与正常对照组小鼠海马神经细胞凋亡发生率[(3.13±1.19)%]和线粒体膜电位[(176.39±13.88)mV]比较,模型组凋亡发生率[(8.06±2.31)%]显著增加(P<0.01)而线粒体膜电位[(97.51±15.73)mV]明显降低(P<0.01);APP17肽治疗组检测结果与正常对照组接近,海马神经细胞凋亡发生率[(4.38±1.26)%]低于模型组(P<0.01),线粒体膜电位[(168.35±19.29)mV]高于模型组(P<0.01)。结论APP695转基因小鼠存在学习和记忆功能障碍,且其海马神经细胞凋亡率增加,线粒体膜电位降低;APP17肽能够明显改善该转基因小鼠的学习和记忆能力,其作用机制可能是通过稳定线粒体膜电位及抑制凋亡发生而实现。     

黄连解毒汤对APP/PS1双转基因阿尔茨海默病模型小鼠脑组织的保护

Huanglian Jiedu decoction(HLJDD) has been shown to improve cerebral blood flow,and reduce lipid peroxidation damage to the brain and its energy metabolism.The present study was designed to observe the cerebroprotective effect of HLJDD on an Alzheimer’s disease rodent model,prese-nilin-1/amyloid protein precursor double transgenic mice.HLJDD reduced serum interleukin-6 and interleukin-1β levels,decreased β-amyloid precursor protein gene and senile plaque expression,resisted oxidation,and reduced free radical-induced injury,thereby improving the learning and memory of these mice.Moreover,HLJDD at 433 mg/kg per day exhibited better effects compared with that at 865 or 216 mg/kg per day,and donepezil hydrochloride at 30 mg/kg per day.Thus,these results suggest that HLJDD may have protective effects against Alzheimer’s disease.     

Comparative study of histopathology changes between the PS1/APP double transgenic mouse model and Aβ1-40 -injected rat model of Alzheimer disease

Objective To identify the genetype of the PS1/APP double transgenie mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenie mice models and Aβ1-40-injeeted rats models of Alzheimer disease. Methods The modified congo red staining, Nissl＇s staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ1-40-intrahippocmnpal-injeeted rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl＇s staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ1-40-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response , while no neurons loss were observed in this model.     

Sensorimotor gating and memory deficits in an APP/PS1 double transgenic mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive deterioration and neuropsychiatric symptoms. Sensorimotor gating deficit has been identified in neuropsychiatric diseases. The aim of the present study was to evaluate the possible sensorimotor gating deficit and its correlation to memory impairment and cerebral β-amyloid (Aβ) plaque deposits in an amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mouse model of AD. The sensorimotor gating in 3-, 7- and-22-month-old non-transgenic and transgenic mice was evaluated in a prepulse inhibition (PPI) task. Results revealed that the PPI was lower in the 7- and 22-month-old transgenic mice compared with the age-matched control, while the response to startle pulse-alone in the transgenic and non-transgenic mice was comparable. Congo red staining showed that Aβ neuropathology of transgenic mice aggravated with age, and the 3-month-old transgenic mice started to have minimum brain Aβ plaques, corresponding to the early stage of AD phenotype. Furthermore, memory impairment in the 7-month-old transgenic mice was detected in a water maze test. These results suggest that the sensorimotor gating is impaired with the progressing of AD phenotype, and its deficit may be correlated to cerebral Aβ neuropathology and memory impairment in the APP/PS1 transgenic mouse model of AD.     

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。     

Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice

The deposition of amyloid beta (Abeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e., human and/or mouse, we performed a histopathological analysis, using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. There was a significant correlation between the human amyloid beta deposits and the intrinsic rodent amyloid beta deposits, that is, all plaques contained both human and mouse Abeta, and the diffuse amyloid beta deposits also colocalized human and mouse Abeta. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human Abeta, and most of these vessels also label with mouse Abeta. Our findings demonstrate that the human amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse Abeta, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human Abeta, whereas the rim of the plaque contains both human and mouse amyloid beta, similarly, human and mouse Abeta are differentially localized in the blood vessel wall. Finally, as early as amyloid beta deposits can be detected, they show the presence of both human and mouse Abeta. Together, these data indicate that mouse Abeta is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human Abeta.     

Increased hippocampal neurogenesis in the progressive stage of Alzheimer's disease phenotype in an APP/PS1 double transgenic mouse model

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with senile β‐amyloid (Aβ) plaques and cognitive decline. Neurogenesis in the adult hippocampus is implicated in regulating learning and memory, and is increased in human postmortem brain of AD patients. However, little is currently known about the changes of hippocampal neurogenesis in the progression of AD. As brain tissues from patients during the progression of AD are generally not available, an amyloid precursor protein (APP)/presenilin1 (PS1) double transgenic mouse model of AD was studied. Bromodeoxyuridine (BrdU) labeling supported by doublecortin staining was used to detect proliferating hippocampal cells in the mice. Compared with age‐matched wild‐type controls, 9‐month‐old transgenic mice with memory impairment and numerous brain Aβ deposits showed increased numbers of proliferating hippocampal cells. However, 3‐month‐old transgenic mice with normal memory and subtle brain Aβ deposits showed normal hippocampal proliferation. Double immunofluorescent labeling with BrdU and either NeuN or glial fibrillary acidic protein was conducted in mice at 10 months (28 days after the last BrdU injection) to determine the differentiation of proliferating cells. The number of hippocampal BrdU‐positive cells and BrdU‐positive cells differentiating into neurons (neurogenesis) in 10‐month‐old mice was greater in transgenic mice compared with age‐matched controls, but the ratio of hippocampal BrdU‐positive cells differentiating into neurons and astroglia was comparable. These results suggest hippocampal neurogenesis may increase during the progression of AD. Targeting this change in neurogenesis and understanding the underlying mechanism could lead to the development of a new treatment to control the progression of AD. © 2009 Wiley‐Liss, Inc.     

Synaptic fatigue is more pronounced in the APP/PS1 transgenic mouse model of Alzheimer's disease

To search for potential mechanism that might alter synaptic transmission following Abeta increase we have examined the presynaptic component of transmitter release. As parameters of synaptic transmission that might underlie presynaptic mechanisms, we have used paired-pulse facilitation (PPF), post-tetanic potentiation (PTP), and synaptic fatigue (SF) at the connection between the hippocampal Schaffer-collateral pathway and CA1 pyramidal neurons in approximately 5 month old double transgenic mice overexpressing the mutated form of amyloid precursor protein (APPK670N, M671L) and presenilin 1 (PS1M146V). While the presynaptic mechanisms of PPF and PTP were not compromised in the APP/PS1 mice, SF was more pronounced in the double transgenic animals. The percentage of the 40th fEPSP slope over the first during the tetanus was 18 -/+ 3% in APP/PS1 vs. 26 -/+ 2% in WT. Thus, it is likely that presynaptic mechanisms underlying SF but not PPF and PTP, may account for synaptic dysfunction in APP/PS1 mice.     

Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease

Alzheimer's disease (AD) is characterised by progressive cognitive impairment with neuropsychiatric symptoms such as anomalous motor behaviour, depression, anxiety, weight loss, irritability and agitation. The effect of hAPP and PS1 overexpression on cognition has been well characterised in a variety of transgenic mouse models, however, non-cognitive behaviours have not been considered as systematically. The non-cognitive behaviour of the hAPP/PS1 transgenic mouse model (TASTPM) was observed at ages spanning the rapid progression of amyloid neuropathology. TASTPM transgenic mice, of both genders, exhibited decreased spontaneous motor activity, disinhibition, increased frequency and duration of feeding bouts, reduced body weight and, by 10 months, increased activity over a 24h period. In addition to the aforementioned behaviours, male transgenic mice also displayed enhanced aggression relative to wildtype controls. These data reveal previously unreported disease relevant behavioural changes that demonstrate the value of measuring behaviour in APP/PS1 transgenic models. These behavioural readouts could be useful in screening putative drug treatments for AD.     

APP／PS1阿尔茨海默病转基因动物模型胼胝体损害研究

目的探讨APP／PS1阿尔茨海默病转基因动物模型胼胝体病理学改变。方法取胼胝体作为白质代表区域,采用氯化金髓鞘染色和轴突免疫组织化学染色方法,利用光密度方法对胼胝体轴突密度和髓鞘化程度的染色进行ROD定量分析。结果年龄相关性分析表明,老年组小鼠（包括APP／PS1和PS1）的轴突密度较年轻组小鼠显著下降,然而老年组小鼠的髓鞘化程度较年轻组有所增高。不同表型分析显示,年轻组APP／PS1小鼠的轴突密度和髓鞘化程度和年轻组PS1小鼠一致,然而老年组APP／PS1小鼠轴突密度和髓鞘化程度较老年组PSI小鼠显著下降。结论在APP／PS1阿尔茨海默病转基因动物模型中胼胝体存在着轴突的丢失和脱髓鞘改变,与β淀粉样蛋白对白质的毒性作用有关。