Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia

• Published in: Acta neuropathologica communications Vol. 7; no. 1; p. 178
• Main Authors: Thal, Dietmar Rudolf, Ronisz, Alicja, Tousseyn, Thomas, Rijal Upadhaya, Ajeet, Balakrishnan, Karthikeyan, Vandenberghe, Rik, Vandenbulcke, Mathieu, von Arnim, Christine A F, Otto, Markus, Beach, Thomas G, Lilja, Johan, Heurling, Kerstin, Chakrabarty, Aruna, Ismail, Azzam, Buckley, Christopher, Smith, Adrian P L, Kumar, Sathish, Farrar, Gill, Walter, Jochen
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14-11-2019; BMC
• Subjects: [F-18]flutemetamol; a-beta; Adult; Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta peptide; Amyloid beta-Peptides - metabolism; Amyloid load; Amyloid maturation; Amyloid PET; Amyloid β peptide; angiopathy; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; cognitive; Cohort Studies; deposition; Female; human brain; Humans; impairment; Insoluble amyloid; Male; Middle Aged; national institute; neurofibrillary tangles; Neurologi; Neurology; neuropathologic assessment; Neurosciences & Neurology; pet; Positron-Emission Tomography - methods; Positron-Emission Tomography - trends; senile plaques; Soluble amyloid; Staging; Amyloid load; Amyloid maturation; Amyloid β peptide; Alzheimer’s disease; Amyloid PET; Staging; [18F]flutemetamol; Insoluble amyloid; Soluble amyloid
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-019-0837-9

Alzheimer's disease (AD)-related amyloid β-peptide (Aβ) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and undergoes qualitative changes in its composition of modified Aβ species throughout the pathogenesis of AD. It is not clear which of these aspects of Aβ pathology contribute to AD progression and to what extent amyloid positron emission tomography (PET) reflects each of these aspects. To address these questions three cohorts of human autopsy cases (in total n = 271) were neuropathologically and biochemically examined for the topographical distribution of Aβ pathology (plaques and CAA), its quantity and its composition. These parameters were compared with neurofibrillary tangle (NFT) and neuritic plaque pathology, the degree of dementia and the results from [
F]flutemetamol amyloid PET imaging in cohort 3. All three aspects of Aβ pathology correlated with one another, the estimation of Aβ pathology by [
F]flutemetamol PET, AD-related NFT pathology, neuritic plaques, and with the degree of dementia. These results show that one aspect of Aβ pathology can be used to predict the other two, and correlates well with the development of dementia, advancing NFT and neuritic plaque pathology. Moreover, amyloid PET estimates all three aspects of Aβ pathology in-vivo. Accordingly, amyloid PET-based estimates for staging of amyloid pathology indicate the progression status of amyloid pathology in general and, in doing so, also of AD pathology. Only 7.75% of our cases deviated from this general association.