Pathological similarity and difference between Alzheimer’s disease<br>and dementia with Lewy bodies

Pathological similarity and difference between Alzheimer's disease
and dementia with Lewy bodies

Kimiko Obi¹⁾, Haruhiko Akiyama²⁾

¹⁾Department of Neurology, Juntendo University School of Medicine
²⁾Tokyo Metropolitan Organization for Medical Research

Aβ and tau accumulate in the brain of dementia with Lewy bodies (DLB) almost similarly to AlzheimerAlzheimer'srsquo;s disease (AD).　There is also a propensity for Aβ to accumulate in Parkinson's disease (PD).　On the other hand, accumulation of α-synuclein, a neuropathological hallmark of PD and DLB, occurs in a significant number of AD patients.　AD patients frequently develop extrapyramidal symptoms while many PD patients develop dementia in later stages of the illness.　Thus, there is both clinical and pathological overlap between PD/DLB and AD.　Recently, some investigators proposed a possible interaction between the aggregation processes of tau and α-synuclein, in which one triggers the other to promote the pathological process synergistically.　Many DLB patients have disproportionately mild tau pathology, but total pathology of tau and α-synuclein is proportionate to Aβ deposition in both AD and DLB.　Aβ seems to promote both tau and α-synuclein aggregation.　The amounts of resultant tau and α-synuclein accumulation may depend on the strength of pathological background that causes aggregation of each molecule.　We propose that the process from Aβ to tau and α-synuclein pathology in AD and DLB could be unified into a single diagram.　If the propensity for tau aggregation predominates, the phenotype shows AD, and, if the propensity for α-synuclein predominates, the pathological cascade is shifted towards PD/DLB.　AD, DLB and PD could be a spectrum of diseases.

Address correspondence to Dr. Kimiko Obi, Department of Neurology, Juntendo University School of Medicine (2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan)