与衰老相关的tau蛋白病变,如额颞叶痴呆(FTD),其变体(如进行性核上性麻痹(PSP),选择疾病(PiD),皮质基底变性(CBD),当然也是最常见的痴呆症,阿尔茨海默病(AD)是广泛认可的tau蛋白病形式。tau蛋白病的名单正在扩大。我们现在包括:(i)Tau蛋白病,其中疾病的原因或触发因素显然是身体上的,例如在创伤性脑损伤(TBI)或慢性创伤性脑病(CTE)中,和(ii)导致tau蛋白病变但在与TAU无关的基因中具有致病性遗传变异的遗传疾病。后者的例子是强直性肌营养不良1型和2型(DM1,DM2,由于基因DMPK和CNBP的致病性遗传变异,分别),尼曼-皮克病C型(NPD,由于NPC1或NPC2中的突变),库夫斯病(CLN6),Christianson综合征(SLC9A6),家族性帕金森病(PD),和许多其他人。就受影响的大脑区域和细胞类型而言,TAU病理/聚集体的细胞内分布,发病年龄,TAU病理的疾病进展和扩散速度,有,然而,在大多数这些疾病实体中很少见。这里,我认为TAU/MAPT是少数tau蛋白病的病因(例如,MAPT相关的FTD/PSP和空泡Tau病(VCP))和其他关键介质,就像AD的压倒性证据所显示的那样。然而,TAU也可能只是旁观者,甚至在其他环境中也可能是保护者。改善对罕见tau蛋白病变的了解对于开发特定的治疗方法是必要的,同时也提高了我们对TAU的病理机制作用的认识,并确定可能从基于TAU的治疗中获益的疾病.
Ageing-associated tauopathies like frontotemporal dementia (FTD), variants thereof (like progressive supranuclear palsy (PSP), pick diseases (PiD), corticobasal degeneration (CBD)), and of course the most prevalent form of dementia, Alzheimer Disease (AD), are widely recognized forms of tauopathies. The list of tauopathies is expanding. We now include: (i) tauopathies where the disease cause or trigger is clearly either physical, such as in Traumatic Brain Injury (TBI) or Chronic Traumatic Encephalopathy (CTE), and (ii) genetic diseases that result in tauopathy but have pathogenic genetic variants in genes not related to TAU. Examples of the latter are myotonic dystrophy Type 1 and Type 2 (DM1, DM2, due to pathogenic genetic variants in the genes DMPK and CNBP, respectively), Niemann-Pick Disease Type C (NPD, due to mutations in NPC1 or NPC2), Kufs Disease (CLN6), Christianson Syndrome (SLC9A6), familial forms of Parkinson Disease (PD), and many others. In terms of affected brain regions and cell types, intracellular distribution of TAU pathology/aggregates, age of disease onset, velocity of disease progression and spreading of TAU pathology, there is, however, little in common in most of these disease entities. Here, I reason that TAU/MAPT is causative for the minority of tauopathies (e.g., MAPT-related FTD/PSP and Vacuolar Tauopathy (VCP)) and a critical mediator for others, like shown by overwhelming evidence for AD. However, TAU may also be a mere bystander or even protective in other settings. Improved understanding of rare tauopathies is necessary to develop specific treatments, but also to improve our understanding of the pathomechanistic role of TAU and to identify diseases that may profit from TAU-based therapies.