Corticobasal degeneration (CBD) is a rare neurodegenerative disorder. The most common presentation of CBD is the corticobasal syndrome (CBS), which is a constellation of cortical and extrapyramidal symptoms and signs. Clinical-pathological studies have illustrated that CBD can present with diverse clinical phenotypes, including a non-fluent, agrammatic primary progressive aphasia syndrome, a behavioral, dysexecutive and visuospatial syndrome, as well as a progressive supranuclear palsy-like syndrome. Conversely, multiple pathologies, such as CBD, Alzheimer's disease and progressive supranuclear palsy may underlie a patient with CBS. This clinical-pathological overlap emphasizes the need for biomarkers that will assist in the accurate diagnosis of patients with CBS. This review presents an overview of the pathological, genetic, clinical and therapeutic characteristics of CBD, with an emphasis on the imaging (structural and functional) and biochemical (cerebrospinal fluid) biomarkers of CBD.

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are nowadays recognized as spectrum disorders with a molecular link, the TAR DNA-binding protein 43 (TDP-43), rendering it a surrogate biomarker for these disorders. Methods: We measured cerebrospinal fluid (CSF) levels of TDP-43, beta-amyloid peptide with 42 amino acids (Aβ42), total tau protein (τT), and tau protein phosphorylated at threonine 181 (τP-181) in 32 patients with ALS, 51 patients with FTD, and 17 healthy controls. Double-sandwich commercial enzyme-linked immunosorbent assays were used for measurements. Results: Both ALS and FTD patients presented with higher TDP-43 and τT levels compared to the control group. The combination of biomarkers in the form of the TDP-43 × τT / τP-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities >0.8. Conclusion: Combined analysis of TDP-43, τT, and τP-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD.

Background: Alzheimer’s disease dementia (ADD) may manifest with atypical phenotypes, resembling behavioral variant frontotemporal dementia (bvFTD) and corticobasal syndrome (CBS), phenotypes which typically have an underlying frontotemporal lobar degeneration with tau proteinopathy (FTLD-tau), such as Pick’s disease, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or FTLD with TDP-43 proteinopathy (FTLD-TDP). CSF biomarkers total and phosphorylated tau (τ_T and τ_P-181), and amyloid beta with 42 and 40 amino acids (Aβ₄₂ and Aβ₄₀) are biomarkers of AD pathology. The primary aim of this study was to compare the diagnostic accuracy of Aβ₄₂ to Aβ₄₂/Aβ₄₀ ratio in: (a) differentiating ADD vs. frontotemporal dementias; (b) patients with AD pathology vs. non-AD pathologies; (c) compare biomarker ratios and composite markers to single CSF biomarkers in the differentiation of AD from FTD; Methods: In total, 263 subjects were included (ADD: n = 98; bvFTD: n = 49; PSP: n = 50; CBD: n = 45; controls: n = 21). CSF biomarkers were measured by commercially available ELISAs (EUROIMMUN). Multiple biomarker ratios (Aβ₄₂/Aβ₄₀; τ_T/τ_P-181; τ_T/Aβ₄₂; τ_P-181/Aβ₄₂) and composite markers (t-tau: τ_T/(Aβ₄₂/Aβ40); p-tau: τ_P-181/(Aβ₄₂/Aβ₄₀) were calculated. ROC curve analysis was performed to compare AUCs of Aβ₄₂ and Aβ₄₂/Aβ₄₀ ratio and relevant composite markers between ADD and FTD, as defined clinically. BIOMARKAPD/ABSI criteria (abnormal τ_T, τ_P-181 Aβ₄₂, and Aβ₄₂/Aβ₄₀ ratio) were used to re-classify all patients into AD pathology vs. non-AD pathologies, and ROC curve analysis was repeated to compare Aβ₄₂ and Aβ₄₂/Aβ₄₀; Results: Aβ₄₂ did not differ from Aβ₄₂/Aβ₄₀ ratio in the differentiation of ADD from FTD (AUCs 0.752 and 0.788 respectively; p = 0.212). The τ_T/Aβ₄₂ ratio provided maximal discrimination between ADD and FTD (AUC:0.893; sensitivity 88.8%, specificity 80%). BIOMARKAPD/ABSI criteria classified 60 patients as having AD pathology and 211 as non-AD. A total of 22 had discrepant results and were excluded. Aβ₄₂/Aβ₄₀ ratio was superior to Aβ₄₂ in the differentiation of AD pathology from non-AD pathology (AUCs: 0.939 and 0.831, respectively; p < 0.001). In general, biomarker ratios and composite markers were superior to single CSF biomarkers in both analyses. Conclusions: Aβ₄₂/Aβ₄₀ ratio is superior to Aβ₄₂ in identifying AD pathology, irrespective of the clinical phenotype. CSF biomarker ratios and composite markers provide higher diagnostic accuracy compared to single CSF biomarkers.

Primary progressive aphasia (PPA) may present with three main clinical variants, namely nonfluent agrammatic (nfaPPA), semantic (sPPA), and logopenic (lPPA) subtypes. Frontotemporal lobar degenerations (FTLD) or Alzheimer's disease (AD) are the most common etiologies. To study the potential of cerebrospinal fluid (CSF) biomarkers for identifying the underlying pathology in patients with PPA. CSF levels of total tau protein (τT), amyloid-β peptide (Aβ42), and tau phosphorylated at threonine-181 (τP - 181) were measured by double sandwich, enzyme-linked immunosorbent assay (ELISA) in 43 patients with PPA, 26 patients with AD, and 17 healthy controls. All patients could be classified as compatible with the AD or non-AD biomarker profile, either with the three biomarkers (90.7%) or their ratios, especially the τP - 181/Aβ42 ratio (9.3%). An AD-compatible biomarker profile was present in 39.5% of all PPA patients, specifically 22.2%, 35.7%, and 75% of nfaPPA, sPPA, and lPPA, respectively. In PPA patients with a non-AD profile (presumably FTLD), two different clusters could be identified according to the τP - 181/τT ratio, possibly corresponding to the two major FTLD pathologies (tau and TDP-43). CSF biomarkers may be a valuable tool for the discrimination between PPA patients with AD and non-AD pathophysiology and possibly between FTLD patients with tau and TDP-43 pathology.

Idiopathic bormal pressure hydrocephalus (iNPH) is a neurological syndrome that clinically presents with Hakim’s triad, namely cognitive impairment, gait disturbances, and urinary incontinence. The fact that iNPH is potentially reversible makes its accurate and early diagnosis of paramount importance. Its main imaging characteristic is the dilation of the brain’s ventricular system and the imaging parameters are also included in its diagnostic criteria along with clinical data. There is a variety of different modalities used and a great number of imaging markers that have been described while assessing iNPH patients. The present literature review attempts to describe the most important of these imaging markers and to shed some light on their role in diagnosis, differential diagnosis, and possibly prognosis of this potentially reversible neurological syndrome.