Hansen Niels, Hirschel Sina, Teegen Bianca, Wiltfang Jens, Malchow Berend
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Translational Psychoneuroscience, University Medical Center Göttingen, Göttingen, Germany.
Front Dement. 2022 Dec 20;1:975851. doi: 10.3389/frdem.2022.975851. eCollection 2022.
Alzheimer's disease (AD) is seldom reported to be associated with neural autoantibodies apart from those involved in axonal neurodegeneration and amyloidopathy in prior studies. Nevertheless, this is an under-investigated aspect of AD. As we do not know whether additional screening for autoantibodies in AD patients has additional diagnostic and therapeutic value, this study aims to shed light on whether visuoconstructive or figural memory capacities might distinguish these patient populations.
In this pilot case series, we investigated eight patients suffering from cognitive impairment associated with cerebrospinal fluid (CSF)-based Alzheimer pathology (AP) and with verified anti-neural autoantibodies (AP Aab+) compared to eight AD patients presenting no autoantibodies (Aab-) (AD Aab-). Patients files were reviewed retrospectively regarding their neuropsychological profile assessed the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery and psychopathology measured by the AMDP (Manual for the Assessment and Documentation of Psychopathology in Psychiatry) system. We also relied on diagnostic parameters as in the CSF and magnetic resonance images.
All patients shared the same pattern of dysfunctional word-list learning and word-list recall resembling a hippocampus-dependent memory dysfunction. Furthermore, both patient groups revealed a CSF profile concurring with Alzheimer's disease. However, visuoconstructive capacity, but not figure recall was preserved in AP Aab+ patients, but not in AD Ab-patients with the shared hippocampus-based memory dysfunction. We observed no relevant differences between the AP Aab+ and AD Aab- groups in CSF cell-counts or intrathecal IgG synthesis. The relative frequency of hippocampal and focal atrophy did not differ either between AP Aab+ and AD Aab- groups.
Our pilot findings are encouraging us to conduct large-scale studies to replicate our discovery of preserved visuoconstruction in AP Aab+ patients with hippocampus-based memory dysfunction. The role of anti-neural autoantibodies is still not fully understood. The detection of these autoantibodies might imply another disease pathology that could be either neuroprotective or be affecting other brain regions, i.e., less pronounced disease activity in the right temporo-parietal regions mainly involved in visuoconstruction.
在先前的研究中，除了那些与轴索性神经变性和淀粉样病变相关的神经自身抗体外，很少有报道称阿尔茨海默病（AD）与神经自身抗体有关。然而，这是AD中一个研究不足的方面。由于我们不知道对AD患者进行额外的自身抗体筛查是否具有额外的诊断和治疗价值，本研究旨在探讨视觉构建或图形记忆能力是否可以区分这些患者群体。
在这个试点病例系列中，我们调查了8例患有与基于脑脊液（CSF）的阿尔茨海默病病理（AP）相关的认知障碍且有经证实的抗神经自身抗体（AP Aab+）的患者，并与8例无自身抗体（Aab-）的AD患者（AD Aab-）进行比较。回顾性审查患者档案，了解其通过阿尔茨海默病注册协会（CERAD）测试套件评估的神经心理学概况以及通过精神病理学评估和记录手册（AMDP）系统测量的精神病理学情况。我们还依据脑脊液和磁共振图像中的诊断参数。
所有患者都有相同的功能失调的单词列表学习和单词列表回忆模式，类似于海马体依赖的记忆功能障碍。此外，两组患者的脑脊液特征均与阿尔茨海默病一致。然而，AP Aab+患者的视觉构建能力得以保留，但图形回忆能力未保留，而具有共同的基于海马体的记忆功能障碍的AD Aab-患者则不然。我们观察到AP Aab+组和AD Aab-组在脑脊液细胞计数或鞘内IgG合成方面没有相关差异。AP Aab+组和AD Aab-组之间海马体和局灶性萎缩的相对频率也没有差异。
我们的初步研究结果鼓励我们开展大规模研究，以重复我们在具有基于海马体的记忆功能障碍的AP Aab+患者中发现的保留视觉构建能力这一发现。抗神经自身抗体的作用仍未完全了解。这些自身抗体的检测可能意味着另一种疾病病理，其可能具有神经保护作用，或者影响其他脑区，即主要参与视觉构建的右侧颞顶叶区域的疾病活动不太明显。
