Similar amyloid-β burden in posterior cortical atrophy and Alzheimer's disease

Abstract

While the clinical presentation of posterior cortical atrophy is clearly distinct from typical Alzheimer's disease, neuropathological studies have suggested that most patients with posterior cortical atrophy have Alzheimer's disease with an atypical visual presentation. We analysed in vivo pathophysiological markers of Alzheimer's disease such as cerebrospinal fluid biomarkers and positron emission tomography imaging with ¹¹C-labelled Pittsburgh compound-B in posterior cortical atrophy to determine whether biochemical profile and fibrillar amyloid-β burden topography are associated with the clinical presentation. Nine patients with posterior cortical atrophy and nine with typical Alzheimer's disease individually matched for age, duration and severity of the disease and 10 cognitively normal age-matched controls were included. ¹¹C-labelled Pittsburgh compound-B images were analysed both using volumes of interest and on a voxel-wise basis using statistical parametric mapping, taking into account the individual regional cortical atrophy. Cerebrospinal fluid biomarkers did not differ between posterior cortical atrophy and patients with Alzheimer's disease. Compared with normal controls, both posterior cortical atrophy and Alzheimer's disease groups showed increased ¹¹C-labelled Pittsburgh compound-B uptake. No significant difference was found in regional or global ¹¹C-labelled Pittsburgh compound-B binding between posterior cortical atrophy and Alzheimer's disease groups with both volumes of interest and voxel-wise basis using statistical parametric mapping methods. Our findings demonstrate that cerebrospinal fluid biomarkers and positron emission tomography imaging with ¹¹C-labelled Pittsburgh compound-B may be useful in identifying an atypical visual form of Alzheimer's disease. The similar topography of fibrillar amyloid-β deposition between typical Alzheimer's disease and posterior cortical atrophy groups suggests that, although amyloid-β accumulation plays a critical role in the pathogenesis of Alzheimer's disease, other factors such as neurofibrillary tangles may contribute to the different clinical features observed in posterior cortical atrophy.

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

“…Previous studies from our group and others using amyloid PET have shown that the distribution of fibrillar amyloid in AD is largely overlapping and is indistinguishable across clinical variants (26,(50)(51)(52)(53). This raises the possibility that network-based degeneration may be driven by other factors, such as oligomeric Aβ (not imaged by current PET ligands) or neurofibrillary tangles.…”

Aphasia with left occipitotemporal hypometabolism: A novel presentation of posterior cortical atrophy?

“…15 Patients with PCA likewise show diffuse PiB retention. 23,24 As with other focal variants of AD, areas of hypometabolism correlate strongly with the focal symptoms, 3,4,18,24 as neurofibrillary tangles may have a strong contribution to the clinical features. 23 In fact, most AD patients presenting with aphasia have an asymmetrical increase in left hemispheric neurofibrillary tangle density as compared to typical AD patients.…”

Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease

“…Previous studies on CSF biomarkers in distinct clinical variants of probable AD have shown that CSF Aβ 42 levels are reduced (reflecting greater amyloid burden) independent of phenotype (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014). In contrast, for CSF t-tau and p-tau results have shown discrepancies between studies.…”

“…In contrast, for CSF t-tau and p-tau results have shown discrepancies between studies. Some studies have found comparable t-tau and p-tau levels between amnestic AD and PCA (Baumann, et al, 2010, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Seguin, et al, 2011), amnestic AD and lvPPA (Santangelo, et al, 2014, Teng, et al, 2014), and between EOAD and LOAD (Bouwman, et al, 2009). One study found lower CSF t-tau and p-tau levels in PCA than in lvPPA and amnestic AD (Teng, et al, 2014) and another study found higher CSF t-tau and p-tau levels in lvPPA compared to amnestic AD (Magnin, et al, 2014).…”