## 4 Discussion  
Atypical presentations of AD have been incorporated in most recent diagnostic criteria. However, recognizing atypical AD patients based on clinical, neuropsychological, or imaging data is difficult. CSF biomarkers represent a reliable tool of AD identification in vivo. Studies on CSF biomarkers in patients with diverse cognitive, behavioral, and/or movement manifestations aiming to identify atypical AD presentations are rare. These studies are important because they highlight the clinical diversity of AD and reiterate the importance of CSF biomarkers in identifying atypical AD phenotypes. In the present study, we retrospectively reviewed the clinical presentations of 98 patients with a typical AD CSF biomarker profile. Roughly half of AD patients presented with the typical amnestic picture. This percentage is much lower compared to the 84% suggested by community-oriented studies [35] and is closer to the 54-63% observed in samples coming from research centers [36; 37]. A selection bias seems to be responsible for this low incidence, since the study was conducted in a tertiary academic center where patients with atypical presentations are usually referred. Additionally, more than half of our patients had early-onset AD, an age group where atypical presentations are known to be overrepresented [38]. Atypical presentations may represent one third of young-onset AD patients [39]. Thus, the relative frequencies observed in the present study do not reflect those of the community, but of specialized research centers. This selection bias is not necessarily a drawback. In fact, it serves as a magnifying lens, allowing better recognition and study of non-amnestic AD presentations. Indeed, in addition to the \"usual atypical\"  
Figure 2: Scatterplot of CSF concentrations of A\(\beta\)42 (**a**), \(\tau_{\text{T}}\) (**b**), and \(\tau_{\text{P-181}}\) (**c**) in AD subgroups. Horizontal broken lines indicate the cut-off values of our laboratory. Horizontal bars indicate median values. For typical presentations, white circles indicate dementia stage and half-filled circles indicate MCI stage. For mixed presentations, black circles indicate mixed with VD and white circles indicate mixed with Lewy bodies. For atypical presentations, upward white triangles indicate frontal, downward white triangles indicate posterior, and white circles indicate logopenic presentations. For other unusual presentations, black triangles indicate PSP-like, white circles indicate non-logopenic PPA, dotted white circles indicate NPH, and white squares indicate CBS presentations. presentations (mixed, frontal, posterior, logopenic), we have identified a small percentage of \"unusual atypical\" presentations not yet recognized in diagnostic or research criteria for AD [13; 14; 15]. Non-logopenic PPA patients with AD have been described in neuropathological [3; 40] and CSF biomarker studies, rendering biomarkers useful in identifying such patients in vivo [19; 41; 42; 43]. Indeed, AD may be the underlying cause not only in more than half (-75-86%) of the patients with logopenic, but also in ~20% of the non-fluent argammatic and ~16-35% of the semantic subtypes of PPA [19; 44]. AD may be the underlying pathology in some of the patients fulfilling even the criteria for probable CBD [4], and, again, the classical CSF biomarkers may be helpful in identifying such patients, who may comprise 30-38% of corticobasal syndrome presentation [45; 46]. Interestingly enough, we observed one patient (1% of our group) with an AD biomarker profile and typical Richardson syndrome presentation. This has been reported previously in up to 10% of PSP patients [46], though it is not clear if they represent atypical presentation of AD or mixed pathology. The existence of mixed cases with NPH has been known for a long time. AD and/or cerebrovascular pathology may be present in a significant percentage of NPH patients, increasing with age [47].