Brain Biopsy Prior to Treatment of Alzheimer's Disease

Abstract

A cortical biopsy was analyzed using immunohistochemical methodology in a total of 213 patients with suspected normal pressure hydrocephalus (NPH). Normal intracranial pressure (ICP) was registered in 121 (43 %) of patients with suspected NPH. The incidence of Alzheimer's disease (AD) related lesions was quite high, since 38 % of all subjects displayed β-amyloid (βA4) aggregates and in 8 % of subjects paired helical filament-tau (PHF-τ) pathology was noted. The AD associated pathologies were more common in subjects with normal than elevated ICP. Of the 121 subjects with NPH, 16 (13 %) had subclinical, histopathologically verified AD and a further 40 subjects (33 %) could be considered to be at high risk to develop AD. Pharmacological treatment trials of AD should be carried out on subjects with evident brain pathology (βA4 aggregates or PHF-τ pathology) especially during the early stage of the disease, i.e., the subclinical stage. For this purpose a simple cortical biopsy with a low risk of complication would represent a diagnostic “method” of choice.

NPH - AD - β-amyloid aggregates - cortical biopsies

References

• 1 Esiri M M, Hyman B T, Beyreuther K, Masters C L. Ageing and dementia. In: Graham DI, Lantos PL (eds). Greenfield's Neuropathology, 6th ed London: Arnold 1997 Vol. 2 Chap. 4. 
• 2 Ince P G, Perry E K, Morris C M. Dementia with Lewy bodies. A distinct non-Alzheimer dementia syndrome?.  Brain Pathology. 1998;  8 299-324
• 3 Parkkien L, Soininen H, Laakso M, Alafuzoff I. α-synuclein pathology is highly dependent on the case selection.  Neuropath Appl Neurobiol. 2001;  27 314-325
• 4 Savolainen S, Paljärvi L, Vapalahti M. Prevalence of Alzheimer's disease in patients investigated for presumed normal pressure hydrocephalus: a clinical and neuropathological study.  Acta Neuropathol. 1999;  141 849-853
• 5 Alafuzoff I, Helisalmi S, Mannermaa A, Riekkinen P, Soininen H. β-Amyloid load is not influenced by the severity of cardiovascular disease in aged and demented patients.  Stroke. 1999;  30 613-618
• 6 Lobo A, Launer L J, Fratiglioni L, Andersen K, di Carlo A, Breteler M M, Copeland J R, Dartigues J F, Jagger C, Martinez.Lage J, Soininen H, Hofman A. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic disease in elderly research group.  Neurology. 2000;  54 S4-9
• 7 Koivisto K. Population based dementia screening program in the city of Kuopio, Eastern Finland. Evaluation of screening methods, prevalence of dementia and dementia subtypes. Series of reports, Department of Neurology Doctoral dissertation. 1995
• 8 Mirra S S, Heyman A, McKeel D, Sumi S M, Crain B J, Brownlee L M, Vogel F S, Highes J P, van Belle G, Berg L. The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease.  Neurology. 1991;  41 479-486
• 9 Bech R A, Waldemar G, Gjerris F, Klinken L, Juhler M. Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.  Acta Neurochir. 1999;  141 633-639
• 10 Golomb J, Wisoff J, Miller D C, Boksay I, Kluger A, Weiner H, Salton J, Graves W. Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response.  J Neurol Neurosurg Psychiatr. 2000;  68 778-781
• 11 Braak H, Braak E. Neuropathological staging of Alzheimer's changes.  Acta Neuropathol. 1991;  82 239-259
• 12 Kudo T, Mima T, Hashimoto R, Nakao K, Morihara T, Tanimukai H, Tsujio I, Koike Y, Tagami S, Mori H, Nakamura Y, Tanaka T, Mori K, Takeda M. Tau protein is a potential biological marker for normal pressure hydrocephalus.  Psychiatry Clin Neurosci. 2000;  54 199-202