TY - JOUR
T1 - Early Alzheimer-type lesions in cognitively normal subjects
AU - Tsartsalis, Stergios
AU - Xekardaki, Aikaterini
AU - Hof, Patrick R.
AU - Kövari, Enikö
AU - Bouras, Constantin
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/2
Y1 - 2018/2
N2 - Amyloid deposits and tau-immunoreactive neurofibrillary tangles, together with neuronal and synaptic loss, are the neuropathological hallmarks of Alzheimer's disease (AD). Both proteins are present in the normal brain during aging. However, the temporal sequence of their involvement in the onset of AD pathology remains controversial. To define whether amyloid β protein deposits or tau protein lesions appear first during normal brain aging, we performed an immunohistological study on serial sections from 105 autopsy brains (age range: 40–104 years) from patients free of clinical signs of cognitive decline, using anti-tau (AT8) and anti-amyloid (4G8) antibodies in the hippocampus, entorhinal cortex, inferior temporal cortex (Brodmann area 20), prefrontal cortex (Brodmann area 9), occipital cortex (Brodmann areas 17 and 18), and in the brainstem. All cases older than 48 years displayed at least a few neurofibrillary tangles, which appeared more frequently in the entorhinal than in the transentorhinal cortex. Tau pathology in these areas preceded tau inclusions in the brainstem. Furthermore, the first site of the apparition of tau pathology is inconsistent, being the entorhinal cortex in most cases, and in fewer cases, the transentorhinal region. There was no case presenting with amyloid deposition in the absence of neurofibrillary tangles, lending evidence to the fact that neurofibrillary tangles appear earlier than amyloid plaques during normal brain aging. However, the role of amyloid in promoting tau deposition cannot be excluded in some cases but may not represent the sole mechanism of disease induction and progression.
AB - Amyloid deposits and tau-immunoreactive neurofibrillary tangles, together with neuronal and synaptic loss, are the neuropathological hallmarks of Alzheimer's disease (AD). Both proteins are present in the normal brain during aging. However, the temporal sequence of their involvement in the onset of AD pathology remains controversial. To define whether amyloid β protein deposits or tau protein lesions appear first during normal brain aging, we performed an immunohistological study on serial sections from 105 autopsy brains (age range: 40–104 years) from patients free of clinical signs of cognitive decline, using anti-tau (AT8) and anti-amyloid (4G8) antibodies in the hippocampus, entorhinal cortex, inferior temporal cortex (Brodmann area 20), prefrontal cortex (Brodmann area 9), occipital cortex (Brodmann areas 17 and 18), and in the brainstem. All cases older than 48 years displayed at least a few neurofibrillary tangles, which appeared more frequently in the entorhinal than in the transentorhinal cortex. Tau pathology in these areas preceded tau inclusions in the brainstem. Furthermore, the first site of the apparition of tau pathology is inconsistent, being the entorhinal cortex in most cases, and in fewer cases, the transentorhinal region. There was no case presenting with amyloid deposition in the absence of neurofibrillary tangles, lending evidence to the fact that neurofibrillary tangles appear earlier than amyloid plaques during normal brain aging. However, the role of amyloid in promoting tau deposition cannot be excluded in some cases but may not represent the sole mechanism of disease induction and progression.
KW - Alzheimer's disease
KW - Amyloid
KW - Brain aging
KW - Neurofibrillary tangle
KW - Primary age-related tauopathy
UR - http://www.scopus.com/inward/record.url?scp=85032664870&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2017.10.002
DO - 10.1016/j.neurobiolaging.2017.10.002
M3 - Article
C2 - 29107845
AN - SCOPUS:85032664870
SN - 0197-4580
VL - 62
SP - 34
EP - 44
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -