Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Aβ peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Aβ peptide, similar but not identical to the Aβ peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Aβ, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Aβ 42 levels, except for the Arctic mutation, which alters the Aβ sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Aβ deposition in most mouse lines. Doubly (APP × mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Aβ. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Aβ oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau −/− background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Aβ or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis.

Charles Duyckaerts

Marie-Claude Potier

Benoît Delatour

Acta Neuropathologica

ACTA NEUROPATHOLOGICA 旨在发表关于神经疾病病理学的最佳论文，以及使用体外和体内模型对分子和细胞机制进行的实验研究，并通过人体组织分析进行理想验证。该期刊发表原创论文、评论文章、案例报告和科学通信（信件）。提交出版的手稿必须包含声明，说明所有人体研究都已由相应的伦理委员会审查，因此已按照适当版本的伦理标准进行1964 年赫尔辛基宣言。还应在正文中明确说明所有人员在纳入研究之前均已签署知情同意书。应省略可能披露研究对象身份的细节。动物实验报告必须说明遵循“实验动物护理原则”（NIH 出版物第 86-23 号，1985 年修订），以及特定的国家适用的法律（例如当前版本的德国动物保护法）。编辑保留拒绝不符合上述要求的稿件的权利。作者将承担虚假陈述或未能满足上述要求的责任。

Acta Neuropathologica aims to publish high-quality papers on the pathology of neurological diseases, including experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, validated through human tissue analysis. The journal accepts original research articles, review articles, case reports, and scientific communications (letters). All submitted manuscripts must include a statement indicating that all human research has been reviewed by the appropriate ethics committee and conducted in accordance with the appropriate version of the ethical standards of the Declaration of Helsinki (1964). Furthermore, the main text should clearly state that all participants signed informed consent prior to inclusion in the study, and details that could disclose the identity of research subjects should be omitted. Reports of animal experiments must indicate adherence to the 'Principles of Laboratory Animal Care' (NIH Publication No. 86-23, revised 1985) and relevant national laws (e.g., the current version of the German Animal Protection Act). The editor reserves the right to reject manuscripts that do not meet these requirements, and authors will be held responsible for false statements or failure to comply with the above requirements.

《Acta Neuropathologica》旨在发表关于神经疾病病理学的高质量论文，涵盖使用体外和体内模型研究分子和细胞机制的实验研究，并通过人体组织分析进行验证。该期刊接受原创论文、评论文章、案例报告和科学通信（信件）。所有提交的手稿必须包含声明，表明所有人体研究均已通过相应伦理委员会的审查，并遵循1964年赫尔辛基宣言的适当版本的伦理标准。此外，正文中应明确说明所有参与者在研究纳入前均已签署知情同意书，且应省略可能揭示研究对象身份的细节。动物实验报告必须说明遵循“实验动物护理原则”（NIH出版物第86-23号，1985年修订）以及适用的国家法律（例如当前版本的德国动物保护法）。编辑有权拒绝不符合上述要求的稿件，作者需对虚假陈述或未能满足上述要求承担责任。

Acta Neuropathol

Alzheimer disease models and human neuropathology: similarities and differences

The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations, and some insight is gained into the kinetics of the changes.

Category	Quartile
医学	1
医学, 临床神经病学	1
医学, 神经科学	1
医学, 病理学	1

Alzheimer disease models and human neuropathology: similarities and differences

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