Clinicopathologic subtype of Alzheimer's disease presenting as corticobasal syndrome

Abstract

Introduction: The corticobasal syndrome (CBS) is associated with several neuropathologic disorders, including corticobasal degeneration and Alzheimer's disease (AD).

Method: In this report, we studied 43 AD patients with CBS (AD-CBS) and compared them with 42 AD patients with typical amnestic syndrome (AD-AS), as well as 15 cases of corticobasal degeneration and CBS pathology.

Results: Unlike AD-AS, AD-CBS had prominent motor problems, including limb apraxia (90%), myoclonus (81%), and gait disorders (70%). Alien limb phenomenon was reported in 26% and cortical sensory loss in 14%. Language problems were also more frequent in AD-CBS, and memory impairment was less frequent. AD-CBS had more tau pathology in perirolandic cortices but less in superior temporal cortex than AD-AS. In addition, AD-CBS had greater neuronal loss in the substantia nigra.

Discussion: AD-CBS is a clinicopathological subtype of AD with an atypical distribution of Alzheimer-type tau pathology. Greater neuronal loss in the substantia nigra may contribute to Parkinsonism which is not a feature of typical AD.

Keywords: Alzheimer's disease; Corticobasal syndrome; Neurodegeneration; Neuropathology; Tau.

Fig. 1.. Clinical features during the disease course of AD-CBS and controls

Data are displayed as frequency of given clinical feature (percent of total in that group). Post hoc pairwise comparison analysis is performed with Mann-Whitney rank sum test. The asterisks (*) indicate significant differences between AD-CBS and CBD-CBS (myoclonus - P=0.006, aphasia = P=0.007, memory impairment; P=0.004, hallucinations or delusions; P=0.01, dystonia; P=0.04, and falls; P=0.03)

Fig. 2.. Macroscopic examples of AD-CBS and AD-AS

Comparison of representative cases of AD-CBS (A, B, C) and AD-AS (D, E, F). The midsagittal view shows marked medial frontal atrophy, especially in paracentral lobule and peri-Rolandic region (MTR) in AD-CBS (A), but not in AD-AS (D). Coronal sections show ventricular enlargement, with disproportionate enlargement of frontal compared with temporal horns of the lateral ventricle in AD-CBS (B) compared with AD-AS (E). Transverse sections of the midbrain show decreased neuromelanin pigment in the lateral substantia nigra (SN) in AD-CBS (C) compared with AD-AS (F).

Fig. 3.. Phospho-tau immunohistochemistry of AD-CBS and AD-AS

Peri-Rolandic cortices of representative cases of AD-CBS (A and D) and AD-AS (B and D) immunostained for phospho-tau. Boxed areas of motor cortex in A and B are shown at higher magnification in C and D. Representative higher magnification images of phospho-tau immunostaining in motor cortex of AD-CBS (E) and AD-AS (F) after application of the image analysis color deconvolution algorithm on the same images in (G) and (H). Strong positive pixels are shown in red. Tau burden is the ratio of strong positive pixels to all pixels in the region of interest. The analysis does not discriminate between NFT and neuropil threads. Note higher density of tau pathology in motor cortex of AD-CBS compared with AD-AS. Scale bars: A - 150-μm, C - 20-μm, E - 50-μm.